Liquid measurement systems, apparatus, and methods optimized with temperature sensing

ABSTRACT

An apparatus for measuring liquid volume in a container includes a plurality of light sources for emitting electromagnetic radiation (EMR) toward the container, a plurality of sensors optically coupleable to the plurality of light sources, each sensor of the plurality of sensors for detecting the EMR emitted by at least a portion of the plurality of light sources, a temperature sensor for measuring at least one temperature associated with a liquid in the container, and at least one processor for receiving data representative of the portion of the detected EMR from each of the plurality of sensors, comparing the at least one measured temperature to a temperature guideline to identify any temperature events associated with the received data; normalizing the received data based on any temperature events associated with the received data; and converting the normalized data into a signature representative of the EMR detected by the plurality of sensors.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to and the benefit of U.S. ProvisionalApplication No. 62/032,017, entitled, “Liquid Measurement System withTemperature Sensor,” filed Aug. 1, 2014, the disclosure of which ishereby incorporated by reference in its entirety.

BACKGROUND

The present disclosure relates generally to systems, apparatus, andmethods for measuring a quantity of a liquid and/or a temperature of theliquid disposed in a delivery device, and in particular to an injectionpen cap that includes a temperature sensor.

Many chronic disease patients are prescribed medications that need to beself-administered, administered by a caregiver, or administered by anautomated or semi-automated delivery system using injection pens orsimilar drug delivery devices. For example, patients diagnosed with TypeI or II diabetes must regularly check their blood glucose levels andadminister an appropriate dose of insulin using an injection pen. Inorder to monitor the efficacy of the medication, dose information mustbe recorded. The process of manually logging dose information,particularly in an uncontrolled setting, is tedious and error prone.Patients often forget to log the dose information when administeringmedicine. In addition, many such patients may be minors or elderly whocannot efficiently and/or accurately track the dose information.

Incomplete dosage records hinder the ability of a patient to self-managedisease conditions and prevent caregivers from adjusting care plansbased on behavioral insights. Lack of adherence to target dosageschedules for injectable medicines may result in an increased need forcritical care, which results in a significant increase in health carecosts in countries around the world.

Thus, a need exists for improved technological aids, in particular, newdelivery devices, to better assist both patients in improving theirability to self-manage disease treatment using drug delivery devices andcaregivers in monitoring patient health. In particular, there is a needfor systems, apparatus, and methods that facilitate data acquisition onpatient behavior and allow that data to be used to reduce the incidenceof hospital visits (e.g., re-admission), as well as to inform andeducate patients, care providers, family members, and financial serviceproviders.

SUMMARY

Embodiments described herein relate generally to systems, apparatus, andmethods for measuring a quantity of a liquid and/or a temperature of theliquid disposed in a delivery device, and in particular to an injectionpen cap that includes a temperature sensor. The inventors haverecognized and appreciated that temperature may affect properties ofembodiments of the systems, apparatus, and methods described herein. Inparticular, temperature may affect measurements of a quantity of aliquid made using some embodiments. In some embodiments, temperature mayaffect properties of one or more additional components, such as aglucose meter test strip.

Temperature may also affect the quality of a drug disposed in a drugdelivery device. The efficacy and shelf life of medications—including,but not limited to, insulin—are highly impacted by the temperature towhich a particular medication is exposed and/or at which a particularmedication is stored. Injection pens that contain such medications areoften carried by a patient, for example, in a patient's pocket,backpack, purse, luggage, etc. Thus, medications may be exposed towidely fluctuating ambient temperatures which can impact the expirationstatus of the medications and/or the bioavailability of, bioefficacy of,and/or comfort provided by the medications as ultimately delivered tothe patient. Furthermore, knowledge of the specific impact oftemperature exposure may allay safety concerns and anxieties ofpatients, care providers, and family members.

In some embodiments, a dose measurement system for measuring a liquidvolume in a container includes a plurality of light sources which aredisposed and configured to emit electromagnetic radiation toward thecontainer. A plurality of sensors is optically coupleable to theplurality of light sources. The sensors are disposed and configured todetect the electromagnetic radiation emitted by at least a portion ofthe light sources. The apparatus includes a temperature sensorconfigured to measure a temperature of the liquid disposed in thecontainer. The apparatus also includes a processing unit configured toreceive data representing the portion of the detected electromagneticradiation from each of the plurality of sensors and to convert thereceived data into a signature representative of the electromagneticradiation detected by the plurality of sensors. The processing unit isalso configured to receive temperature information from the temperaturesensor and normalize sensor values, determine an efficacy of the liquid,determine an expiration status of the liquid, determine a level ofadministration comfort, etc. In some embodiments, the temperature sensoris also configured to measure the temperature of the environmentsurrounding the liquid.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic block diagram of a dose measurement system inaccordance with some embodiments.

FIG. 2 is a perspective view of a dose measurement system in accordancewith some embodiments.

FIG. 3 is an exploded perspective view of the dose measurement system ofFIG. 2 in accordance with some embodiments.

FIG. 4 is a top exploded top view of the dose measurement system of FIG.2 in accordance with some embodiments.

FIG. 5 is a schematic illustration of a communications interface thatmay be included in the dose measurement system of FIG. 2 in accordancewith some embodiments.

FIG. 6 is a schematic ray diagram of different modes of lighttransmission between a first medium and a second medium in accordancewith some embodiments.

FIG. 7 is a cross-sectional view of a dose measurement system inaccordance with some embodiments.

FIG. 8 is a cross-sectional view of a dose measurement system inaccordance with some embodiments.

FIG. 9 is a cross-sectional view of a dose measurement system inaccordance with some embodiments.

FIG. 10 is a side cross-sectional view of a dose measurement system inaccordance with some embodiments.

FIGS. 11A-11C are cross-sectional views of a dose measurement system ina first, second, and third configuration, respectively, in accordancewith some embodiments.

FIG. 12 is a cross-sectional view of the dose measurement system of FIG.11A, taken along line A-A, in accordance with some embodiments.

FIG. 13 is a cross-sectional view of the dose measurement system of FIG.11C, taken along line B-B, in accordance with some embodiments.

FIG. 14 is a graph showing reference signature signals of sensors of adose measurement system in accordance with some embodiments.

FIG. 15 is a flow diagram of a method of operation of the dosemeasurement system in accordance with some embodiments.

FIG. 16 is a flow diagram of a method of operation of the dosemeasurement system in accordance with some embodiments.

FIG. 17 is a schematic block diagram of a health management systemassociated with a dose measurement system in accordance with someembodiments.

FIG. 18 is a schematic block diagram of a liquid measurement system witha temperature sensing module in accordance with some embodiments.

FIG. 19 is a perspective view of a liquid measurement system with atemperature sensing module in accordance with some embodiments.

FIG. 20 is an exploded perspective view of the liquid measurement systemof FIG. 19 in accordance with some embodiments.

FIG. 21 shows a back perspective view of a bottom housing included inthe liquid measurement system of FIG. 20 in accordance with someembodiments.

FIG. 22 is a bottom view of a PCB included in a sensing assembly of theliquid measurement system of FIG. 21 in accordance with someembodiments.

FIG. 23 is a graph showing compensated and uncompensated measurements ofa representative sensor of a liquid measurement system as a function oftemperature in accordance with some embodiments.

FIG. 24 is a diagram of part of a liquid measurement system including atemperature sensor in accordance with some embodiments.

FIG. 25 is a screenshot of a user interface display for monitoring oneor more liquid measurement systems in accordance with some embodiments.

DETAILED DESCRIPTION

Embodiments described herein relate generally to systems, apparatus, andmethods for measuring a quantity of a liquid and/or a temperature of theliquid disposed in a delivery device, and in particular to an injectionpen cap that includes a temperature sensor. Many chronic diseasepatients are prescribed medications that need to be self-administered,administered by a caregiver, or administered by an automated orsemi-automated delivery system using injection pens or similar drugdelivery devices. For example, patients diagnosed with Type I or IIdiabetes must regularly check their blood glucose levels and administeran appropriate dose of insulin using an injection pen. In order tomonitor the efficacy of the medication, dose information must berecorded. The process of manually logging dose information, particularlyin an uncontrolled setting, is tedious and error prone.

Furthermore, temperature may affect measurement properties of someembodiments and quality properties of a drug included in someembodiments. The efficacy and shelf life of medications—including, butnot limited to, insulin—are highly impacted by the temperature to whicha particular medication is exposed and/or at which a particularmedication is stored. Injection pens that contain such medications areoften carried by a patient, for example, in a patient's pocket,backpack, purse, luggage, etc. Thus, medications may be exposed towidely fluctuating ambient temperatures which can impact the expirationstatus of the medications and/or the bioavailability of, bioefficacy of,and/or comfort provided by the medications as ultimately delivered tothe patient. Furthermore, knowledge of the specific impact oftemperature exposure may allay safety concerns and anxieties ofpatients, care providers, and family members.

Embodiments of the systems, apparatus, and methods described hereininclude one or more temperature sensors configured to measure atemperature of the liquid disposed in the container and/or anenvironment around the liquid including, but not limited to, a containercontaining the liquid, such as an injection pen.

In some embodiments, a dose measurement system for measuring the liquidvolume in a container includes a plurality of light sources which aredisposed and configured to emit electromagnetic radiation toward thecontainer. The plurality of light sources may include a plurality of,for example, light-emitting diodes (LEDs). Alternatively, a single lightsource (e.g., a single LED) may be used to emit electromagneticradiation into a light pipe that splits the emitted electromagneticradiation into the plurality of light sources which are disposed andconfigured to emit electromagnetic radiation toward the container. Insome embodiments, a plurality of sensors is optically coupleable to theplurality of light sources and is disposed and configured to detect theelectromagnetic radiation emitted by at least a portion of the lightsources. The apparatus also includes a processing unit configured toreceive data representing the portion of the detected electromagneticradiation from each of the plurality of sensors and to convert thereceived data into a signature representative of the electromagneticradiation detected by the plurality of sensors. One or more temperaturesensors are disposed and configured to measure a temperature of theliquid disposed in the container and/or a temperature of the environmentsurrounding the container. This temperature information may be used todetermine a variety of metrics including a level of bioavailabilityand/or bioefficacy of the remaining liquid.

In some embodiments, a method of estimating a volume of liquid in a drugdelivery device includes causing a plurality of light sources to emitelectromagnetic radiation toward a drug container and detecting asignature of the emitted electromagnetic radiation through the drugcontainer with a plurality of sensors. The detected signature is thencompared to a plurality of reference signatures to determine the volumeof liquid in the drug container. Each of the plurality of referencesignatures correspond to a volume level remaining in the drug container.In some embodiments, detecting the signature of the emittedelectromagnetic radiation through the drug container includes detectingat least a portion of the electromagnetic radiation emitted from atleast a portion of the plurality of light sources. The portion of theelectromagnetic radiation detected by each of the plurality of sensordevices may be compiled into the signal signature. In some embodiments,the method further includes detecting one or more temperatures of thedrug, the container, and/or the environment surrounding the container.One or more detected temperatures may be used to indicate a qualityassociated with the drug. One or more temperatures also may be used toindicate a quality associated with and/or adjust volume measurementproperties.

In some embodiments, the method also includes calculating a dosedelivered to a patient based on the volume of liquid in the drugcontainer. In some embodiments, the dose delivered to a patient iscompared with a patient medication schedule to monitor compliance. Themethod may further include correcting the signal signature forbackground light which can contribute to noise. The correction mayinclude comparing the signal signature with a background signaturedetected by the plurality of sensors in a dark state of each of theplurality of light sources. The method may further include correctingthe signal signature for temperature effects. The correction may includecomparing the signal signature with a background signature detected bythe plurality of sensors in a preferred temperature state of each of theplurality of light sources. In some embodiments, the method alsoincludes generating the plurality of reference signatures by recordingthe signature for a range of dose volumes in the drug container. Themethod may also include associating the signal with the referencesignature using probabilistic matching to determine the volume of liquidremaining in the dose container.

In some embodiments, a method for determining a dose delivered by aninjection pen using the drug measurement system includes causing aplurality of light sources to emit electromagnetic radiation toward theinjection pen a first time and detecting a first signature of theemitted electromagnetic radiation through the injection pen with aplurality of sensors. The first signature is then compared to aplurality of reference signatures to determine the first volume ofliquid in the injection pen. The method further includes causing theplurality of light sources to emit electromagnetic radiation toward theinjection pen a second time, after the first time, and detecting asecond signature of the emitted electromagnetic radiation through theinjection pen with the plurality of sensors. The second signature isthen compared to the plurality of reference signatures to determine thesecond volume of liquid in the injection pen. The second volume may bededucted from the first volume to determine a dose delivered from theinjection pen.

In some embodiments, the plurality of light sources and the plurality ofsensors are disposed in an injection pen cap. In some embodiments, themethod includes detecting the first signature prior to the injection pencap being removed from the injection pen and detecting the secondsignature after the injection pen cap has been placed back on theinjection pen. The method may also include communicating the dosedelivered information to an external device. In some embodiments, themethod includes switching the pen cap to a power save mode after apredetermined period of inactivity of the pen cap. In some embodiments,the method further includes alerting the user if a volume of liquidremaining in the drug container is critically low and/or if it is timeto deliver a dose of medication.

In some embodiments, a health management system includes a drug deliverydevice including a drug reservoir, and a dose measurement systemconfigured to be removably coupleable to the drug delivery device. Thedose measurement system includes a plurality of light sources disposedand configured to emit electromagnetic radiation toward the drugreservoir a plurality of sensors optically coupleable to the pluralityof light sources disposed and configured to detect a quantity ofelectromagnetic radiation communicated through the drug reservoir. Thequantity of electromagnetic radiation serves as a signaturerepresentative of the volume of liquid remaining in the drug reservoir.The health management system also includes a display configured topresent information to a user indicative of the volume of liquidremaining in the drug reservoir. The dose measurement system may beconfigured to communicate data representative of the volume of liquidremaining in the drug reservoir to a remote device, for example, toallow the remote device to calculate a dose delivered to the patient. Insome embodiments, the dose management system is configured to receiveuser health data from the remote device which may include, for exampleuser blood glucose level, user diet, user exercise, and/or user homehealth monitored data.

FIG. 1 is a schematic block diagram of a dose measurement system 100 formeasuring the dose in a drug delivery device 110 according to someembodiments. The dose measurement system 100 includes a lighting module140, a sensing module 150, a processing unit 160 and a communicationsmodule 170. The dose measurement system 100 may be configured to beremovably coupleable to the drug delivery device 110 that is used todeliver a drug dose to a target T such as, for example, a human patient.

The drug delivery device 110 may be any drug delivery device 110 thatcan be used for injecting a medication into a patient. For example, thedrug delivery device 110 may be an injection pen (e.g., insulininjection pen), a syringe, pump (e.g., insulin delivery pump), anampoule, or a vial. The dose measurement system 100 may be configured tobe coupleable to a wide variety of drug delivery devices 110 (e.g.,different shapes, sizes, and drug volumes). In some embodiments, thedose measurement system 100 may be configured to receive a portion ofthe drug delivery device 110 (e.g., a portion that defines an internalvolume containing the drug, an injector, and/or plunger). In someembodiments, the dose measurement system 100 is configured to beremovable from the drug delivery device 110 when the user is deliveringa dose to the target T. In some embodiments, the dose measurement system110 may remain attached to the drug delivery device 110 when the user isdelivering a dose to the target T. In some embodiments, the dosemeasurement system 100 is configured to be reusable. In someembodiments, the dose measurement system 110 may be permanently coupledto the drug delivery device 110, for example, integrated into the bodyof the drug delivery device. In such embodiments, the dose measurementsystem 100 may be disposable.

The lighting module 140 includes a plurality of light sources configuredto emit electromagnetic radiation towards the drug delivery device 110.In some embodiments, the plurality of light sources may be configured toemit electromagnetic radiation towards a drug reservoir (not shown) ofthe drug delivery device 110. In some embodiments, each of the pluralityof light sources may be a light emitting diode (LED). In someembodiments, the plurality of light sources may be configured to emitsuch that the electromagnetic radiation can penetrate through housingand any internal components of the drug delivery device 110, and/or theliquid drug contained therein. In some embodiments, the plurality oflight sources may be configured to emit continuous electromagneticradiation for a predefined time period. In some embodiments, theplurality of light sources may be configured to emit pulses ofelectromagnetic radiation (e.g., a series of less than 100 microsecondpulses).

The sensing module 150 includes a plurality of sensors that areoptically coupleable to the plurality of light sources of the lightingmodule 140. In some embodiments, the each of the plurality of sensors isa photodetector. The plurality of sensors are disposed and configured todetect the electromagnetic radiation emitted by at least a portion ofthe light sources. In some embodiments, the detected electromagneticradiation includes transmitted, refracted and reflected portions of theelectromagnetic radiation. In some embodiments, the refractedelectromagnetic radiation may include multi-directional refractioncaused by a lensing effect of a curved surface of the housing of thedrug delivery device 110 and/or the drug reservoir.

The processing unit 160 is configured to receive the electromagneticradiation signal from the sensing module 150 (i.e., each of theplurality of sensors) and convert the received data into a signalsignature representative of the electromagnetic radiation detected byeach of the plurality of sensors. The processing unit 160 may include aprocessor, including, but not limited to, a microcontroller, amicroprocessor, an ASIC chip, an ARM chip, an analog to digitalconvertor (ADC), and/or a programmable logic controller (PLC). In someembodiments, the processing unit 160 may include a memory that isconfigured to temporarily store at least one of the electromagneticradiation data detected by each of the plurality of sensors and thesignal signature produced from it. In some embodiments, the memory mayalso be configured to store a plurality of reference signatures. Each ofthe plurality of reference signatures may be representative of a drugvolume in the drug delivery device 110. In some embodiments, theprocessing unit 160 also includes an RFID chip configured to storeinformation (e.g., the dose remaining information) and allow a nearfield communication (NFC) device to read the stored information. In someembodiments, the processing unit 160 is configured to associate thesignal signature with the reference signature to determine the dosevolume remaining in and/or dose injected by the drug delivery device110. In some embodiments, the processing unit 160 also includes a globalpositioning, infrared radiation, and/or microwave radiation navigationsystem (e.g., GPS) to determine a current location of the dosemeasurement system 100.

The communications module 170 may be configured to allow two-waycommunication with an external device, including, but not limited to, asmart phone, a local computer, and/or a remote server. In someembodiments, the communications module 170 includes means for wirelesscommunication with an external device, including, but not limited to,Wi-Fi, Bluetooth®, low powered Bluetooth®, ZigBee, and the like. In someembodiments, the communications module 170 includes a communicationinterface to provide wired communication with an external device (e.g.,a USB or firewire interface). In some embodiments, the communicationinterface also is used to recharge a power source such as a rechargeablebattery.

In some embodiments, the communications module 170 includes a displayconfigured to communicate a status of the dose measurement system 100 tothe user, including, but not limited to, dose remaining, history of use,remaining battery life, wireless connectivity status, and/or userreminders. In some embodiments, the communications module also includesspeakers and/or vibration mechanisms to convey audio and/or tactilealerts. In some embodiments, the communications module 170 includes auser input interface (e.g., a button, a switch, an alphanumeric keypad,a touch screen, a camera, and/or a microphone) to allow a user to inputinformation or instructions into the dose measurement system 100,including, but not limited to, powering ON the system, powering OFF thesystem, resetting the system, manually inputting details of a patientbehavior, manually inputting details of drug delivery device 110 usage,and/or manually initiating communication between the dose measurementsystem 100 and a remote device.

The dose measurement system 100 may be disposed in a housing (not shown)that is configured to be removably coupleable to the drug deliverydevice 110. For example, the lighting module 140, sensing module 150,processing unit 160 and the communications module 170 may beincorporated into a housing, or individual components of the dosemeasurement system 100 (e.g., the lighting module 140 and the sensingmodule 150) may be incorporated into a first housing and othercomponents (e.g., the processing unit 160 and communications module 170)may be separate or incorporated into a second housing. In someembodiments, the housing is configured (e.g., shaped and sized) to beremovably coupled to at least a portion of the drug delivery device 110.For example, the housing may have a recess and/or define a bore intowhich a portion of the drug delivery device 110 may be received. Thehousing may have alignment features to allow the dose measurement system100 to be coupled to the drug delivery device 110 in a predeterminedradial orientation. The housing may be opaque and include an insulationstructure to prevent interference from ambient electromagnetic radiationto, for example, increase signal quality. For example, the insulationstructure may be a metal lining configured to shield the electroniccomponents of the dose measurement system 100 from externalelectromagnetic radiation. In some embodiments, the housingsubstantially resembles, for example, a pen cap to act as a replacementcap for the drug delivery device 110 (i.e., an injection pen).

In some embodiments, the lighting module 140 and the sensing module 150are disposed and/or oriented in the housing of the dose measurementsystem 100, such that the plurality of light sources are disposed on afirst side, and the plurality of sensors are disposed on a second sideof the drug delivery device 110. In some embodiments, the plurality oflight sources is disposed at a first radial position with respect to thedrug delivery device 110 and the plurality of sensors is disposed at asecond radial position which is different than the first radial position(e.g., the second radial position may be approximately 180 degrees fromthe first radial position). In other words, the dose management system100 may be arranged so that the plurality of light sources is disposedon one side of a drug reservoir and the plurality of sensors is disposedon the opposite side of the drug reservoir. In some embodiments, each ofthe plurality of light sources and the plurality of sensors is disposedin a substantially straight line. In some embodiments, the plurality oflight sources are disposed such that each light source is locatedadjacent to at least one sensor, each light source also located parallelto and in line of sight of at least one sensor. In some embodiments, atleast one of the plurality of light sources and/or at least one of theplurality of sensors is located in an inclined orientation with respectto a longitudinal axis of the drug delivery device 110. In someembodiments, the number of the plurality of sensors is equal to, greaterthan or less than the number of the plurality of light sources. In someembodiments, the plurality of light sources and the plurality of sensorsis configured such that the dose measurement system 110 can detect thevolume of drug in the drug delivery device 110 with a resolution of 1unit of drug or smaller (e.g., fractions of units of drug such as 0.1units, 0.2 units, 0.5 units, etc.). In some embodiments, the pluralityof light sources and the plurality of sensors are configured such thatthe dose measurement system 110 can detect the position of a plungerportion of an actuator disposed in the drug delivery device 110 with aresolution of 10 micrometers, 20 micrometers, 30 micrometers, 40micrometers, 50 micrometers, 60 micrometers, 70 micrometers, 80micrometers, 90 micrometers, 100 micrometers, 110 micrometers, 120micrometers, 130 micrometers, 140 micrometers, 150 micrometers, 160micrometers, 170 micrometers, 180 micrometers, or 200 micrometers,inclusive of all ranges there between.

Having described above various general principles, several exemplaryembodiments of these concepts are now described. These embodiments areonly examples, and many other configurations of a dose measurementsystem, systems and/or methods for measuring dose delivered by a drugdelivery device and overall health of a patient are envisioned.

Referring now to FIGS. 2-4, dose measurement system 200 may include alighting module 240, a sensing module 250, a processing unit 260, acommunications module 270, and a power source 286 according to someembodiments. Dose measurement system 200 may be configured to beremovably coupleable to a drug delivery device 210 (also referred toherein as “an injection pen 210”). Drug delivery device 210 may beconfigured to deliver a predefined quantity of a drug (e.g., a dose) toa patient. Examples of drug delivery device 210 include insulininjection pens that may be used by a patient to self-administer insulin.As described herein, drug delivery device 210 may include a housing 212,an actuator 214, and an injector 216. Housing 212 may be relativelyopaque, such that it only allows select wavelengths of electromagneticradiation (e.g., infrared or microwave radiation) to be transmittedthere through. Housing 212 defines an internal volume (e.g., reservoir)for storing a drug. Actuator 214 may include a plunger portion in fluidcommunication with the drug and configured to communicate a predefinedquantity of drug to the patient. Actuator 214 may be configurable by,for example, the user, to dispense variable quantities of the drug.Injector 216 is configured to penetrate a user's skin for intramuscular,subcutaneous, and/or intravenous delivery of the drug.

Dose measurement system 200 includes a housing 220 that includes a tophousing portion 222 (also referred to herein as “top housing 222”) and abottom housing portion 224 (also referred to herein as “bottom housing224”). Top housing portion 222 and bottom housing portion 224 may beremovably or fixedly coupled together by, for example, gluing, hotwelding, and/or using a snap-fit mechanism, using a screw, or by anyother suitable coupling means. Housing 220 may be made from a rigid,lightweight, and/or opaque material, including, but not limited to,polytetrafluoroethylene, high density polyethylene, polycarbonate, otherplastics, acrylic, sheet metal, and any other suitable material or acombination thereof. Housing 220 also may be configured to shield theinternal electronic components of dose measurement system 200 fromenvironmental electromagnetic noise. For example, the housing mayinclude an insulation structure (not shown) such as, for example, analuminum lining or any other metal sheet or foil that can serve as anelectromagnetic shield.

As shown in FIG. 3, top housing portion 222 defines an internal volumefor substantially housing the lighting module 240, the sensing module250, processing unit 260, communications module 270 and the power source286 according to some embodiments. Bottom housing portion 224 includesdefines a bore 226, shaped and sized to receive at least a portion ofdrug delivery device 210. For example, bore 226 may be shaped and sizedto receive only the drug containing portion of housing 212 and injector216. Bore 226 may be configured to receive drug delivery device 210 in apreferred orientation, such as a preferred radial orientation. In someembodiments, bore 226 is in close tolerance with the diameter of drugdelivery device 210 to, for example, form a friction fit with drugdelivery device 210. In some embodiments, bore 226 includes one or morenotches, grooves, detents, any other snap-fit mechanism, or threads, forremovably coupling drug delivery device 210 to the bottom housing 224.In some embodiments, bottom housing portion 224 includes one or morealignment features to allow drug delivery device 210 to be coupleablewith dose measurement system 200 in a predetermined radial orientation.

In some embodiments, the bottom housing 224 includes one or moreapertures 228 for receiving at least a portion of the plurality of lightsources 244 of the lighting module 240, and/or sensors 254 of thesensing module 250. The apertures 228 may be configured to providemechanical support for the light sources 244 and/or sensors 254, or mayserve as an alignment mechanism for the lighting module 240 and/orsensing module 250.

As shown in FIG. 4, the top housing 222 includes an opening 230 forreceiving at least a portion of communications module 270 such as, forexample, a communication interface to provide wired communication withan external device, and/or an interface for charging the power source286 according to some embodiments. In some embodiments, the top housing222 also includes one or more features (e.g., recesses, apertures,cavities, etc.) for receiving a portion of drug delivery device 210 suchas injector 216. In some embodiments, housing 220 also includes adetection mechanism (not shown) to detect if drug delivery device 210has been coupled to dose measurement system 200. The detection mechanismmay include, but is not limited to, a push switch, a motion sensor, aposition sensor, an optical sensor, a piezoelectric sensor, an impedancesensor, or any other suitable sensor. Housing 220 may be relativelysmooth and free of sharp edges. In some embodiments, housing 220 isshaped to resemble a pen cap that has a form factor that occupiesminimal space (e.g., fitting in a user's pocket). In some embodiments,housing 220 also includes an attachment feature (e.g., a clip forattaching to a user's pocket or belt) and/or an ornamental feature. Insome embodiments, dose measurement system 200 also serves as areplacement cap for drug delivery device 210.

Referring still to FIGS. 3 and 4, the plurality of light sources 244(e.g., a plurality of LEDs or a single LED connected to a light pipesplitting emitted electromagnetic radiation into the plurality of lightsources) of the lighting module 240 are mounted on, or otherwisedisposed on, a printed circuit board (PCB) 242. The PCB 242 may be anystandard PCB made by any commonly known process. In some embodiments,the plurality of light sources 244 is arranged in a straight line andequally spaced such that, when the portion of drug delivery device 210that defines the internal volume of housing 212 holding the drug iscoupled with dose measurement system 200, the light sources 244illuminate the entire internal volume. In some embodiments, the lightsources 244 are placed in any other configuration, including, but notlimited to, a zig-zag configuration, an unequally spaced configuration,a staggered configuration, a configuration in which the light sources244 are alternately disposed with the sensors 254, and/or any otherconfiguration as described herein.

In some embodiments, the light sources 244 are configured to produce anelectromagnetic radiation of a wavelength that is capable of penetratingthrough housing 212 of drug delivery device 210, the drug containedtherein, and/or a portion of housing 220. For example, infraredradiation or microwave radiation can penetrate many of the plasticmaterials that are commonly used in manufacturing drug delivery devices(e.g., injection pens). In some embodiments, an electromagneticradiation has a frequency that also penetrates through the internalcomponents of drug delivery device 210 (e.g., the plunger portion ofactuator 214). In some embodiments, each of the light sources 244 isconfigured to produce a wide angle beam of electromagnetic radiation(e.g., a plurality of wide angle LEDs or a single LED connected to alight pipe configured to produce a plurality of wide angleelectromagnetic radiation beams). Said another way, the electromagneticradiation cone of a single light source 244 may have a wide angle, andthe electromagnetic radiation cones of adjacent light sources 244 mayoverlap. In some embodiments, the plurality of light sources 244 areconfigured to emit pulses of electromagnetic radiation (e.g., a seriesof less than 100 microsecond pulses).

The plurality of sensors 254 of the sensing module 250 are mounted on,or otherwise disposed on, a PCB 252. The PCB 252 may be any standard PCBmade by any commonly known process. The plurality of sensors 254 may beany optical sensors (e.g., photodiodes) optically coupleable with theplurality of light sources 244 and configured to detect at least aportion of the electromagnetic radiation emitted by the plurality oflight sources 244. The electromagnetic radiation may be transmittedradiation (e.g., transmitted through air, drug, and/or body of drugdelivery device 210), refracted radiation (e.g., refracted by air, drug,and/or body of drug delivery device 210), reflected radiation (e.g.,reflected from a wall of housing 220 or internally reflected from a wallof drug delivery device 210), and/or multi-directionalrefraction/reflection caused by a lensing effect of a curved surface ofhousing 212 and/or the drug reservoir. The transmitted, refracted,and/or reflected electromagnetic signal received by the plurality ofsensors 254 may be used to create a signal signature (e.g., byprocessing unit 260). For example, the signal signature may then beassociated with a reference signature to determine the dose remaining indrug delivery device 210. In some embodiments, the signal response ofthe sensors 254 may be used to measure usability metrics such as, forexample, determining the presence of injector 216 of drug deliverydevice 210, and/or determining whether drug delivery device 210 iscoupled/uncoupled to dose measurement system 200. In some embodiments,the sensors 254 are arranged in a substantially similar configuration tothe light sources 244. In some embodiments, the number of sensors 254 isgreater or less than the number of light sources 244. In someembodiments, the light sources 244 and sensors 254 are arranged suchthat each PCB 244, 254 includes a combination of light sources 244 andsensor 254 (e.g., arranged alternatively). In some embodiments, thelight sources 244 and/or sensors 254 are arranged in an inclinedorientation.

Processing unit 260 may include a PCB 262 and a processor 264. The PCB262 may be any standard PCB made by any commonly known process and mayinclude amplifiers, transistors and/or any other electronic circuitry asnecessary. The processor 264 may be any processor, including, but notlimited to, a microprocessor, a microcontroller, a PLC, an ASIC chip, anARM chip, an ADC, or any other suitable processor. Processing unit 260may be coupled to the lighting module 240 and the sensing module 250using electronic couplings 266, such that the lighting module 240 andthe sensing module 250 are oriented perpendicular to processing unit 260and parallel to each other. In some embodiments, processing unit 260includes an onboard memory for at least temporarily storing a signalsignature, a reference signature database, dose information, user healthdata (e.g., blood glucose level), device location data (e.g., from a GPSreceiver optionally included in dose measurement system 200 or fromanother GPS-enabled device that is communicatively coupled with thesystem 200 such as a blood glucose meter or a cellular phone), and anyother data as might be useful for a patient to manage their health. Insome embodiments, processing unit 260 includes an RFID chip configuredto store information and allow an NFC device to read the informationstored therein. Processing unit 260 may be configurable to control theoperation of dose measurement system 200, for example, activation andtiming of the light sources 244, and/or reading and processing ofelectromagnetic radiation data from the sensors 254. For example,processing unit 260 may be configured to compare electromagneticradiation signal signature obtained from the plurality of sensors 254and associate it with the reference signature database to determine thequantity of dose remaining in drug delivery device 210 or the positionof actuator 214 (e.g., a plunger) of drug delivery device 210.

In some embodiments, processing unit 260 is configured to correct thesignal signature for background noise. For example, processing unit 260may be configured to operate the sensing module 250 to detect abackground signature with the lighting module in dark state, i.e., eachof the plurality of light sources 244 switched off. The backgroundsignature may be associated with the signal signature to correct forbackground noise. In some embodiments, processing unit 260 also includeselectronic signal filtering algorithms, including, but not limited to, aFourier transform, a low pass filter, a band pass filter, a high passfilter, a Bessel filter, and/or any other digital filter to reduce noiseand increase signal quality. Processing unit 260 also may be configuredto obtain reference signatures by storing the electromagnetic radiationsignal detected by the sensing module 250 for a range of dose volumes ina representative drug delivery device 210, including, but not limitedto, full, empty, and/or a series of intervals there between (e.g., everyunit of dose dispensed from the drug delivery device and/or every 170micrometer displacement of a plunger portion of actuator 214 included indrug delivery device 210).

In some embodiments, processing unit 260 is configured to includeprobabilistic matching algorithms that can be used to associate thesignal signature with the reference signature to determine a volume ofliquid in drug delivery device 210. Processing unit 260 also may beconfigured to control and operate communications module 270. In someembodiments, processing unit 260 is configured to operate the system ina power efficient manner. For example, processing unit 260 may turn offat least some of the electronics powering the light sources 244 (e.g.,an operational amplifier) when not needed. Processing unit 260 may pulsethe light sources 244 for a short period at high current to, forexample, save power and/or increase signal-to-noise ratio. Processingunit 260 also may be configured to periodically activate communicationsmodule 270, including, but not limited to, a predetermined number oftimes per day (e.g., ten times) and/or when dose measurement system 200is attached to drug delivery device 210. Processing unit 260 also may beconfigured to deactivate communications module 270 when it is notneeded. In some embodiments, processing unit 260 also includes a globalpositioning/navigation system (e.g., GPS) to, for example, determine acurrent location of dose measurement system 200.

Communications module 270 may be configured to communicate data to theuser and/or an external device, for example, a smart phone application,a local computer, and/or a remote server. The communicated data mayinclude, but is not limited to, initial system activation, systemON/OFF, coupling/uncoupling of a drug delivery device, dose remaining,dose history, time, system and/or drug temperature, system location(e.g., GPS), drug delivery device 210 data, drug expiration data,velocity at which drug is delivered, device collisions, device powerremaining, step count, tampering with the system, and/or any other userhealth information or other usable data. In some embodiments,communications module 270 also is configured to receive data, forexample, new calibration data, firmware updates, user health information(e.g., blood glucose, diet, exercise, and/or dose information), and/orany other information input by the user and/or communicated from anexternal device. Communications module 270 may include conventionalelectronics for data communication and may use a standard communicationprotocol, including, but not limited to, Wi-Fi, Bluetooth®, low poweredBlue-tooth®, ZigBee, USB, firewire, and/or NFC (e.g., infrared). In someembodiments, communications module 270 is configured to periodicallyconnect (e.g., ten times per day) to an external device (e.g., a smartphone) to log any dose data stored in the onboard memory. In someembodiments, communications module 270 is activated/deactivated ondemand by the user.

Referring now also to FIG. 5, communications module 270 may include acommunication interface 271 located on an external surface of thehousing 210 of dose measurement system 200 for communicating with theuser according to some embodiments. Communication interface 271 mayinclude a switch 272 (e.g., a power switch, a reset button, and/oranother communication switch) to manually initiate communication with anexternal device (e.g., activate Bluetooth®). In some embodiments, thecommunications interface 271 also includes an indicator 274 such as alight source (e.g., an LED) to indicate to the user, for example, ifdose measurement system 200 is ON/OFF or if communication module 270 isactive. In some embodiments, communication interface 271 includes adisplay 276 for visual communication of information to the user,including, but not limiting to, a dose remaining 278 in drug deliverydevice 210, a current time 280, system power remaining 282, dose history284 (e.g., average dose usage, time last dose taken, etc.), and/or awireless connectivity status. In some embodiments, the communicationsinterface 271 includes an input component (e.g., an alphanumeric keypadand/or a touch screen) to allow a user to input information (e.g., foodintake, exercise data, etc.) into dose measurement system 200. In someembodiments, communications module 270 includes a speaker for providingaudible alerts or messages to the user (e.g., dose reminders and/orreinforcement messages) and/or a microphone for receiving audio inputfrom the user. In some embodiments, communications module 270 includesmeans for tactile alerts (e.g., a vibration mechanism). In someembodiments, communications module 270 communicates other informationpertaining to user health (e.g., steps taken, calories burned, bloodglucose levels, etc.).

The power source 286 may be any power source that can be used to powerdose measurement system 200. In some embodiments, the power source 286includes a disposable battery. In some embodiments, the power source 286includes a rechargeable battery (e.g., a NiCad battery, a Li-ionbattery, a Li-polymer battery, or any other battery that has a smallform factor, such as the types used in cell phones) and/or does not tobe charged frequently (e.g., once per month). In some embodiments, thepower source 286 is charged using an external power source (e.g., thougha power socket located on housing 220 or through a communicationinterface of communications module 270, such as a wired USB interface orvia wireless charging). In some embodiments, the power source 286 ischarged using solar energy and includes solar panels. In someembodiments, the power source 286 is charged using kinetic energy andincludes mechanical energy transducers.

As described above, the plurality of sensors 254 of the sensing module250 are configured to receive at least one of transmitted radiation,refracted radiation (e.g., refracted by air, liquid drug, housing 212 ofdrug delivery device 210), reflected radiation (e.g., reflected from awall of housing 220 or internally reflected from a wall of the internalvolume of drug delivery device 210), and multi-directionalreflection/refraction caused by a lensing effect of a curved surface ofhousing 212 of drug delivery device 210.

Referring now to FIG. 6, a light source L (e.g., a wide angle lightsource) may produce a plurality of light rays emanating and divergingaway from the light source according to some embodiments. The lightsource L is present in a first medium M1 (e.g., air) having a firstrefractive index n1. A second medium M2 (e.g., liquid drug) having asecond refractive index n2, is bordered by the first medium M1 on bothsides. The second refractive index n2 is greater than the firstrefractive index n1 (i.e., n2>n1). The second medium M2 also includes anopaque surface (e.g., a sidewall).

A first light ray L1 emitted by the light source L is incident on theinterface of the first medium M1 and the second medium M2 at a firstangle of degrees. This light ray does not bend as it penetrates throughthe second medium M2 and transmits back into the first medium M1 at theoriginal angle of incidence (i.e., transmitted light).

A second light ray L2 is incident on the interface of the first mediumM1 and the second medium M2 at a second angle greater than zero degrees.The second light ray L2 bends or refracts as it penetrates the secondmedium M2, and then bends again to its original angle of incidence as itreenters the first medium M1, parallel to but offset from the emittedray L2 (i.e., refracted light).

A third light ray L3 is incident on the interface of the first medium M1and the second medium M2 at a third angle greater than the second angle.At this angle of incidence, the light ray L3 does not penetrate into thesecond medium M2 but is reflected back into the first medium M1, suchthat angle of reflection is equal to the angle of incidence (i.e.,reflected light).

A fourth light ray L4 is incident on the interface of the first mediumM1 and the second medium M2 at a fourth angle less than the third angle,such that the light ray L4 refracts in the second medium M2, but is nowincident on the opaque surface included in the second medium M2 (i.e.,reflection from an opaque surface). At least a portion of the light rayL4 is reflected back into the second medium M2, which then reenters backinto the first medium M1 at a fifth angle, such that the fifth angle isnot equal to the fourth angle.

As described herein, the electromagnetic radiation signal received bythe plurality of sensors 254 of the sensing module 250 may include acombination of the transmitted, refracted and reflected portions of theelectromagnetic radiation. A unique signal signature is produced by thecombination of the portions of the electromagnetic radiation atdifferent dose volumes remaining, and/or the actuator 216 position ofdrug delivery device 210. This signal signature may be compared with areference signal signature database (also referred to herein as a“calibration curve”) to obtain the volume of dose remaining in drugdelivery device 210, as described in further detail herein.

Referring now to FIGS. 7-10, various configurations of the light sourcesand the sensors are shown and described according to some embodiments.While the transmitted and reflected portion of the electromagneticradiation emitted by the light sources is shown, the refractive portionis not shown for clarity. As shown in FIG. 7, a dose measurement system300 includes a plurality of light sources 344 and a plurality of sensors354. A drug delivery device 310 is coupled to the dose measurementsystem 300 according to some embodiments. The drug delivery device 310includes a housing 312 and an actuator 314 that collectively define aninternal volume (e.g., a reservoir) for containing a drug. The drugdelivery device 310 also includes an injector 316 for administering thedrug to a patient. The dose measurement system 300 is configured suchthat the plurality of light sources 344 are disposed on a first side ofthe housing oriented towards the drug delivery device 310 and theplurality of sensors 354 are disposed on a second side of the housingsuch that each of the plurality of sensors 354 is substantially oppositeto, and in optical communication with, at least one of the plurality oflight sources 344. In some embodiments, the plurality of light sources344 and/or the plurality of sensors 354 is disposed in a substantiallylinear relationship (e.g., a straight line) with respect to each other.Each of the plurality of sensors 354 receive a combination oftransmitted, refracted, and/or reflected electromagnetic radiationemitted by the plurality of light sources 344. The reflection portion ofthe electromagnetic radiation may be reflected from a plunger portion ofthe actuator 314, and/or reflected from a housing of the dosemeasurement system 300 or the housing 312 of the drug delivery device310. The refraction may be from the housing 312 and/or from the liquiddrug disposed in the drug delivery device 310. The combination of thetransmitted, reflected and refracted portions of the electromagneticradiation detected by each of the plurality of sensors yields a uniquesignal signature for a range of dose volumes remaining in the drugdelivery device 310.

In some embodiments, a plurality of light sources and a plurality ofsensors are alternately disposed on both sides of a drug deliverydevice. As shown in FIG. 8, a dose measurement system 400 may include aplurality of light sources 444 and a plurality of sensors 454 accordingto some embodiments. The drug delivery device 410 includes a housing 412and an actuator 414 that collectively define an internal volume (e.g., areservoir) for containing a drug. The drug delivery device 410 alsoincludes an injector 416 for communicating the drug to a patient. Thedose measurement system 400 is configured such that the plurality oflight sources 444 and the plurality of sensors 454 are disposed on bothsides of the drug delivery device. In other words, each side of the drugdelivery device 410 has a plurality of light sources 444 and a pluralityof sensors 454. This may be advantageous as emission and detection ofelectromagnetic radiation is now performed from both sides of the drugdelivery device 410, which can, for example, remove any biases.

In some embodiments, at least a portion of the plurality of lightsources and/or the plurality of sensors is arranged in an angularorientation. As shown in FIG. 9, a dose measurement system 500 includesa plurality of light sources 544 and a plurality of sensors 554according to some embodiments. The drug delivery device 510 includes ahousing 512 and an actuator 514 that collectively define an internalvolume (e.g., a reservoir) for containing a drug. The drug deliverydevice 510 also includes an injector 516 for communicating the drug to apatient. The dose measurement system 500 is configured such that theplurality of light sources 544 and the plurality of sensors 554 aredisposed on both side of the drug delivery device 510 and have anangular orientation with respect to a longitudinal axis of the dosemeasurement system 500 and drug delivery device 510. This orientationmay ensure that the electromagnetic radiation emitted by the pluralityof light sources 544 is incident on a larger portion of the drugdelivery device 510 than is achievable with the light sources 544oriented in a straight line. Similarly, the plurality of sensors 554also may detect a greater portion of the electromagnetic radiation. Thiscan, for example, result in higher resolution of the sensors 554, and/orreduce the quantity of light sources 544 and/or sensors 554 required toachieve the desired resolution.

In some embodiments, wider angle light sources (e.g., wide angle LEDs ora single LED connected to a light pipe splitting emitted electromagneticradiation into a plurality of wide angle beams), for example, also maybe used ensure that the electromagnetic radiation emitted by theplurality of light sources 544 is incident on a larger portion of thedrug delivery device 510 than is achievable with a narrower beam lightsources 544. In other words, with a wider beam emitted by the lightsources 544, a higher proportion of the overall drug delivery device 510(or of the drug reservoir) is in optical communication with the lightsources 544. Since a higher proportion of the delivery device 510 is inoptical communication with the light sources 544, a broader spectrum ofelectromagnetic radiation being transmitted, reflected and/or refractedthrough the drug delivery device can increase the signal strengthdetectable by the plurality of sensors 554. Said other way, variabilityin the signal signatures (as opposed to increased intensity of lightincident on the sensor) increases with the broadening of the beam oflight incident on the delivery device, therefore increasing theresolution of the dose measurement system 500. For example, wider anglesmay increase ability to distinguish states of the drug delivery device,even though the overall intensity of light may be lower. This is becausedistinguishing states is more about optimizing how the intensity oflight changes from state to state than it is about the absoluteintensity of light.

In some embodiments, a dose measurement system is configured to detect asignal signature from a location of an actuator of a drug deliverydevice, which may be used to estimate the dose remaining in the drugdelivery device. As shown in FIG. 10, a dose measurement system 600includes a plurality of light sources 644 and a plurality of sensors 654according to some embodiments. A drug delivery device 610 is coupled tothe dose measurement system 600. The drug delivery device 610 includes ahousing 612 and an actuator 614 that collectively define an interiorvolume (e.g. a reservoir) for containing a drug. The dose measurementsystem 600 is disposed generally about the actuator 614 portion of thedrug delivery device 610 as opposed to the dose measurement systems 300,400 and 500 being disposed generally around the drug reservoir as shownin FIGS. 7-9. The plurality of light sources 644 and sensors 654 areconfigured and arranged in a substantially similar way as describedabove with reference to FIG. 7. Electromagnetic radiation emitted by theplurality of light sources 644 may be transmitted unblocked by theactuator 614, blocked by a plunger portion of the actuator 614,reflected by a body or the plunger portion of the actuator 614 and/orreflected/refracted by the housing the drug delivery device 610. Thecombination of the transmitted, reflected and refracted portions of theelectromagnetic radiation detected by the plurality of sensors 654 arethen used to generate a signal signature at a given position of theactuator 614. Displacement of the actuator 614 from a first position toa second position changes the transmission, reflection and refractionpattern of the electromagnetic radiation detected by the sensors 654,creating a unique signal signature at each position of the actuator 614.This signature may be correlated to the dose volume remaining in thedrug delivery device 610 (e.g., by association with a referencesignature).

Referring now to FIGS. 11A-11C, each sensor of the plurality of sensorsof a dose measurement system may detect electromagnetic radiationemitted by at least a portion of the plurality of light sources, and thedetected electromagnetic radiation may be a combination of transmittedreflected and refracted electromagnetic radiation. As shown, the dosemeasurement system 700 includes two light sources 744 a and 744 b, andtwo sensors 754 a and 754 b for clarity. The dose measurement system 700is coupled to a drug delivery device 710 which includes a housing 712and an actuator 714 that collectively define an internal volume (e.g., areservoir) for containing a liquid drug. The drug reservoir and at leasta plunger portion of actuator 714 are disposed substantially inside thedose measurement system 700 between the light sources 744 a, 744 b andsensors 754 a, 754 b.

As shown in FIG. 11A, the plunger portion of actuator 714 is in a firstposition (“position 1”) such that the plunger portion is not in the lineof sight of light sources 744 a and 744 b and sensors 754 a and 754 baccording to some embodiments. When electromagnetic radiation is emittedby the light sources 744 a and 744 b towards drug delivery device 710, asignificant portion of the electromagnetic radiation is detected by thesensors 754 a and 754 b in position 1. The electromagnetic radiation mayinclude transmitted radiation, reflected radiation (reflected by, e.g.,housing 712 of drug delivery device 710), and refracted radiation(refracted by, e.g., the liquid drug and/or housing 712), andmulti-direction reflected/refracted radiation (caused by, e.g., a curvedsurface of housing 712 of drug delivery device 710) as described in moredetail below. As shown in this example, sensor 754 a value is 15.3 andsensor 754 b value is 13.7, which indicates that a significant portionof the electromagnetic radiation is detected by the sensors 754 a and754 b.

As shown in FIG. 11B, actuator 714 is displaced to a second position(“position 2”) such that the plunger portion partially blocks the lineof sight between light source 744 b and sensor 754 b according to someembodiments. In position 2, a significant portion of the electromagneticradiation emitted by light source 744 b is blocked from reaching sensor754 b by actuator 714, but at least a portion of the electromagneticradiation emitted by light source 744 a can still reach sensor 754 balong with any multi-directional reflected/refracted electromagneticradiation. Furthermore, sensor 754 a can receive refractedelectromagnetic radiation from sensor 744 b and transmitted, refractedradiation from sensor 744 a. Sensor 754 a also receives electromagneticradiation reflected by a surface of the plunger that at least partiallydefines the drug reservoir. Therefore, at position 2 sensor 754 adetects an electromagnetic radiation value of 15.5 (greater than atposition 1), and sensor 754 b detects an electromagnetic radiation valueof 8.8 (less than at position 1). The unique values measured at position2 can serve as the signal signature values for position 2.

As shown in FIG. 11C, the plunger portion of actuator 714 is in a thirdposition (“position 3”) such that the plunger portion of actuator 714completely blocks the line of sight of the sensor 754 a from theelectromagnetic radiation emitted by light source 744 a, such thatsubstantially no transmitted and or reflected radiation from lightsource 744 a can reach the sensor 754 a according to some embodiments. Aportion of the transmitted electromagnetic radiation emitted by lightsource 744 b is also blocked by at least a portion of actuator 714, fromreaching sensor 754 b. Both the sensors 754 a and 754 b can stillreceive at least a portion of the reflected and refracted portions ofthe electromagnetic radiation emitted by any of the light sources 744 aand/or 744 b. Therefore, at position 3 the sensor 754 a detects anelectromagnetic radiation value of 2.2 (less than at positions 1 and 2),and sensor 754 b detects an electromagnetic radiation value of 12.0(less than at position 1, but greater than at position 2). The uniquevalues measured at position 3 may serve as the signal signature valuesfor position 3.

Referring now to FIG. 12, a cross-section of the dose measurement system700 taken along line AA in FIG. 11A illustrates the lensing effectcaused by the curvature of the drug reservoir according to someembodiments. As shown, a light ray emitted at a zero degree angle bylight source 744 b is transmitted without bending towards sensor 754 b.Two more light rays emitted by light source 744 b, at an angle away fromthe transmitted ray, are caused to refract (i.e., bend) toward thetransmitted ray as they enter the drug reservoir because the liquid drughas a higher refractive index than air. This phenomenon is referred toherein as “a lensing effect,” which can result in focusing of the lightrays toward sensor 754 b. A fourth ray is emitted at an angle furtheraway from the transmitted ray such that it refracts at the air/druginterface, and then is further reflected by an internal surface ofhousing 712 of the drug delivery system 710 such that it is incident onsensor 754 b. A fifth ray is emitted at an angle, such that even afterrefraction it is not incident on sensor 754 b. As described above, thecombination of these rays yields a detected electromagnetic radiationvalue of 15.3 by sensor 754 a and 13.7 by sensor 754 b. These uniquevalues measured at position 1 may serve as the signal signature valuesfor position 1.

Referring now to FIG. 13, a cross-section of the dose measurement system700 taken along line BB in FIG. 11C illustrates effects of actuator 714on the transmission of light according to some embodiments. As shown, alight ray emitted at a zero degree angle by light source 744 b isblocked by a portion of actuator 714. Two more light rays emitted bylight source 744 b, at an angle away from the transmitted ray, passunderacted (refraction through the housing is ignored) through theportion of housing 712 of drug delivery device 710 (i.e., no drug existsin this portion of device 710) and are incident on sensor 754 b. Afourth ray is emitted by light source 744 b at an angle, such that it isinternally reflected by housing 712 and is incident on sensor 754 b,while a fifth ray is internally reflected by housing 712 but is notincident on sensor 754 b. The combination of these rays yields adetected electromagnetic radiation value of 2.2 by sensor 754 a and 12.0by sensor 754 b. These unique values measured at position 3 can serve asthe signal signature values for position 3. It is to be noted thatalthough the line of sight of sensor 754 a is completely blocked fromlight source 744 a, reflected and refracted portions of theelectromagnetic radiation still contribute to generation of a positivevalue.

Although the sensor values for particular positions are described asbeing absolute values, individual sensor values relative to other sensorvalues may be used to infer and/or determine a volume of liquidremaining in the drug reservoir. For example, if sensor 754 a has aparticular value that is different from sensor 754 b value by a certainamount or a certain percentage, it may be indicative of a position/drugvolume remaining in a drug delivery device. Furthermore, a sensor valuerelative to two or more other sensor values may be used to generate acalibration curve of a drug delivery device.

A unique signal signature obtained at various configurations pertainingto the volume of dose dispensed by a drug delivery device may be used toobtain a reference signature (calibration curve) of the dose measurementsystem. FIG. 14 is a graph showing examples of reference signalsignatures obtained for a drug delivery device using a dose measurementsystem that includes a total of seven sensors according to someembodiments. The dose measurement system may be any dose measurementsystem as described herein. The electromagnetic radiation signaturedetected by each of the plurality of sensors for a range of dose volumesdispensed is stored and used to create the reference signature. As canbe seen from the reference signature when the drug delivery device isalmost full, sensor 1 records low amplitude of electromagneticradiation, while sensor 7 records very high amplitude of electrode andall other sensors detect some intermediate signal signature. Incontrast, when the drug delivery is completely empty, sensor 1 recordsvery high amplitude of electromagnetic radiation, while sensor 7 recordslow amplitude and all other sensors detect some intermediate signalsignature.

Sensor 8 detects a uniform sensor signal for a substantial portion ofthe dose delivered, until the almost all the dose has been delivered orthe drug delivery device is almost empty. In some embodiments, thesensor 8 is used as the volume critically low sensor (e.g., to indicatethat the drug delivery device is completely empty). In some embodiments,sensor 8 also is used as a usability metric sensor to detect, forexample, if a drug delivery device is coupled to the dose measurementsystem and/or if a component (e.g., an injector) to be included in thedrug delivery device is present or not.

Therefore in this manner, the signal value recorded from all sensors fora range of drug volumes remaining yields the signal signature for theentire volume of drug in the drug delivery device. The range of drugvolumes used for obtaining the signal signature may include, but is notlimited to, completely full, completely empty, and/or a sufficientnumber of intermediate signatures (e.g., obtained every unit of thetotal fluid dispensed and/or inclusive of all percentages therebetween).

In some embodiments, a reference signature may be corrected forbackground light. For example, a background signature may be detected bydetecting the signal signature from the plurality of sensors in a darkstate of the plurality of light sources. The signal signature may becompared with the background signature to remove background noise. Insome embodiments, the signal signature is associated with the referencesignature to determine a drug volume in the drug delivery device, usingprobabilistic matching algorithms. In some embodiments, the plurality oflight sources and the plurality of sensors are configured such that thedose measurement system can detect a volume of drug in the drug deliverydevice with a resolution of 1 unit of drug, and/or a position of aplunger portion of an actuator disposed in the drug delivery device witha resolution of 100 micrometers, 110 micrometers, 120 micrometers, 130micrometers, 140 micrometers, 150 micrometers, 160 micrometers, 170micrometers, 180 micrometers, or 200 micrometers, inclusive of allranges there between.

FIG. 15 a flow diagram illustrating a method 800 for measuring doseremaining in a drug delivery device using any of the dose measurementsystems described herein according to some embodiments. In step 802, auser attaches a dose measurement system to a drug delivery device. Instep 804, a plurality of sensors disposed in the dose measurement systemscan the drug delivery device to determine the dose remaining. Forexample, a processing unit of the dose measurement system may associatethe signal signature detected by the plurality of sensors with areference signature to determine the dose remaining. In step 806, thesensor data may be recorded on an onboard memory (e.g., an RFID chipand/or a memory that is part of the processing unit of the dosemeasurement system). In step 808, the dose measurement system may alertthe user if the dose remaining is critically low. Audio, visual, and/ortactile indications may be used to alert the user.

In step 810, communications module of the dose measurement system maysearch for an external device (e.g., a smart phone, a local computer, aremote server, etc.). For example, a Bluetooth® connection may beactivated to search for an external device. If the dose measurementsystem pairs with an external device, in step 812, the system may logdose remaining data on the external device and/or receive any firmwareupdates.

Optionally, the dose measurement system also may alert a user when it istime to take a dose, as in step 814. After dose data has been recordedand transmitted to an external device, the user can remove the dosemeasurement system from the drug delivery device in step 816. The userthen may administer (e.g., inject) a pre-determined volume of the doseusing drug delivery device in step 818. In step 820, the user finallyreplaces the dose measurement system on drug delivery device. At whichpoint, method 800 may be repeated.

FIG. 16 is a flow diagram illustrating a method 900 for conserving powerwhen the dose measurement system is not in use according to someembodiments. The method 900 described herein may be used with any of thedose measurement systems described herein. In a first step, a detectionmechanism of the dose measurement system checks for a drug deliverydevice 902. The drug delivery device can either be coupled or uncoupledto the dose measurement system 904. If the drug delivery device is notattached, the dose measurement system automatically checks foroutstanding data in the memory to be logged to an external device or theuser can activate a communications module of the dose measurement system906. In some embodiments, the communications module is only activatedwhen the dose measurement system is attached to a drug delivery device.The dose measurement system then determines if there is onboard data tobe logged and if an external device was found 908. If there is noonboard data to be logged and no external device was found, the dosemeasurement system goes into a power save mode for a predefined time “X”910. For example, a processing unit of the system cans turn off acommunications module of the dose measurement system and/or turn off theelectronics controlling a plurality of light sources and/or plurality ofsensors of the dose measurement system. Time “X” may be, e.g., 1 minute,10 minutes, 1 hour, or any time there between. Alternatively, if thereis data to be logged and an external device was found, the dosemeasurement system pairs with the external device and logs data on theexternal device and/or receives any firmware updates from the externaldevice 912. The dose measurement system can then go into the power savemode 910. If instead a drug delivery device was found to be attached tothe dose measurement system 904, the dose measurement system scans thedrug delivery device and collects signal from all of the plurality ofsensors 914. The signal from each of the plurality of sensors may beused to create a signal signature corresponding to the dose remaining inthe drug delivery device. A processing unit of the dose measurementsystem compares the signal signature with a reference signature toestimate dose remaining in the drug delivery device 916. The dosemeasurement system determines if the dose injected was greater than zero918. If the dose injected was greater than zero, the dose measurementsystem time stamps and stores the dose on an onboard memory 920. Thedose measurement system then goes into the power save mode for the time“X” 910. If the dose injected was not greater than zero 918, than thedose measurement system directly goes into the power save mode for thetime “X” 910.

In some embodiments, any of the dose measurement systems describedherein may be associated with a health management system to manage thehealth of a patient suffering from Type I or II diabetes. FIG. 17 showsa schematic block diagram of a health management system 1000 formanaging the health of a diabetic user U according to some embodiments.The health management system may be a mobile application for using, forexample, on a smart phone, tablet, or portable computer. In someembodiments, the health management system is a local computer or aremote server.

The health management system may be in two-way communication with a dosemeasurement system 1100 that is reversibly coupled to a drug deliverydevice 1110. The drug delivery device 1110 may be an insulin injectionpen or syringe for administering insulin to user U. The dose measurementsystem also may communicate information to a user or receive an inputfrom the user. The health management system 1000 may be configured toreceive the user exercise data E and diet data D. The health managementsystem 1000 also may be configured to receive blood glucose data from ablood glucose sensor 1200. The health management system 1000 further may be configured to receive user health data from a home health monitor1300, e.g., weight, blood pressure, EKG, oxygen saturation, autographymeasures, pulmonary function, water retention, temperature, etc. Thehealth management system 1000 may be in two-way communication with anetwork 1400.

The network may be, for example, a remote server or a call center. Thenetwork 1400 also may be in two ways communication with a monitor M andan authorized drug dispenser DD. The monitor M may be, for example, adoctor, a caregiver, a pharmacy, and/or a clinical trial manager. Theauthorized drug dispenser DD may be, for example, a pharmacy or aclinical trial manager.

In some embodiments, the dose measurement system 1100 communicates tothe health management system the insulin dose remaining in and/or theinsulin dose delivered to user U by the drug delivery device 1110. Insome embodiments, the health management system also includes a memoryfor storing user U insulin dose regimen and/or any other medicationschedule. User U medication regimen may be communicated to the healthmanagement system 1100 by, for example, the monitor M and/or theauthorized drug dispenser DD through the network 1400. In someembodiments, the health management system 1100 also may be used toprocess user U health data, for example, user U blood glucose levels,exercise data E, diet data D, and/or home health monitored data todetermine the status of patient health. In some embodiments, the healthmanagement system 1000 also is configured to compare dose delivered to apatient with a patient medication schedule to monitor compliance.

In some embodiments, the health management system can communicate theuser health and dose information to the monitor M through the network1400. The monitor M can analyze user U's health data and determine ifany changes to the patient medication plan, for example, insulin and/orany other medication dosage needs to be made. If a change is required,in some embodiments, the monitor M can communicate any changes to userU's medication regimen to the authorized drug dispenser DD. In someembodiments, the monitor M also communicates this information to thehealth management system 1100 through the network 1400. In someembodiments, the health management system 1100 can update and store userU's medication regimen and also communicate to the dose measurementsystem 1100, user U's new medication regimen. User U can then access thedose measurement system 1400 to obtain the new measurement plan, forexample, new insulin dosage.

In this manner, user U's health may be monitored, user U's diabetes maybe managed, and user U's medication schedule may be dynamicallypersonalized to user U. In some embodiments, health management systemalso communicates user U health and medication history on a periodicbasis. The health and medication history may be used, for example, toinform user U of any changes that need to be made to improve user U'soverall health. The medication history also may be communicated to themonitor M to analyze user U's progressive health.

Embodiments of the liquid measurement system described herein mayinclude one or more temperature sensors configured to measure atemperature of a liquid and/or a temperature of an environment aroundthe liquid, for example, a temperature of a drug or medication (e.g.,insulin) contained within a container (e.g., an injection pen), thecontainer, and/or ambient air around the container. Knowledge of thetemperature of the liquid may enable determination of one or moreproperties of the liquid, including, but not limited to, a level ofbioavailability and/or bioefficacy of one or more active components ofthe liquid, an expiration status of the liquid, and an ease of use ofthe liquid (e.g., a level of comfort during and following administrationof a drug or medication), as well as allow normalization of liquidvolume data to compensate for changes or fluctuations in volume of theliquid due to temperature changes or fluctuations. A liquid measurementsystem that includes one or more temperature sensors as described hereinmay be any suitable liquid measurement system, for example, an injectionpen cap configured to be used with an injection pen (e.g., an insulininjection pen). Examples of such liquid measurement systems aredescribed in the following sources, which are incorporated herein byreference in their entirety:

-   -   1. U.S. Pat. No. 8,817,258, entitled “Dose Measurement System        and Method,” filed Mar. 12, 2013, as U.S. patent application        Ser. No. 13/796,889, and issued Aug. 26, 2014;    -   2. U.S. patent application Ser. No. 14/334,181, entitled “Dose        Measurement System and Method,” filed Jul. 17, 2014;    -   3. U.S. Patent Application No. 62/032,017, entitled “Liquid        Measurement System with Temperature Sensor,” filed Aug. 1, 2014;        and    -   4. U.S. patent application Ser. No. 14/548,679, entitled “Dose        Measurement System and Method,” filed Nov. 20, 2014.

Embodiments of the liquid measurement system described herein provideseveral advantages including, but not limited to: (1) enabling real-timemeasurement of a temperature of a liquid including disposed in a liquidcontainer, for example, a medication and/or its surrounding environment;(2) using temperature information to determine one or more properties ofthe liquid disposed within the liquid container including, for example,the efficacy, expiration status, ease of administration, or any otherphysical and/or chemical property of the liquid; (3) providing one ormore indications or alerts if a temperature is above or below apredetermined, recommended, and/or allowed range; (4) trackingcumulative exposure of one or more active chemical components of theliquid to heat as it relates to the chemical kinetics of itsdegradation; and (5) optimizing measurements (e.g., dose volume data orblood glucose data) by compensating for temperature artifacts, forexample, normalizing data based on real time temperature measurements toensure that the data is substantially free of any temperature artifacts.

In some embodiments, a liquid measurement system for measuring a liquidvolume in a container includes a plurality of light sources which aredisposed and configured to emit electromagnetic radiation toward thecontainer. A plurality of sensors are optically coupleable to theplurality of light sources and are disposed and configured to detect theelectromagnetic radiation emitted by at least a portion of the lightsources. The apparatus includes a temperature sensor configured tomeasure a temperature of the liquid disposed in the container. Theapparatus also includes a processing unit configured to receive datarepresenting the portion of the detected electromagnetic radiation fromeach of the plurality of sensors and to convert the received data into asignature representative of the electromagnetic radiation detected bythe plurality of sensors. The processing unit of the apparatus describedabove also is configured to receive temperature information from thetemperature sensor and at least one of normalize sensor values,determine efficacy of the liquid, determine expiration status of theliquid, and determine level of administration comfort. In someembodiments, the temperature sensor also is configured to measure thetemperature of the environment surrounding the liquid.

FIG. 18 is a schematic block diagram of a liquid measurement system 1800(also referred to herein as a “dose measurement system”) for measuringthe volume of liquid remaining (also referred to herein as “dose”) in adrug delivery device 1802 according to some embodiments. Dosemeasurement system 1800 includes a lighting module 1804, a sensingmodule 1806, a processing unit 1808, a temperature sensing module 1810,and a communications module 1812. Dose measurement system 1800 may beconfigured to be removably coupleable to drug delivery device 1802,which is used to administer a drug dose to a target T, such as, forexample, a human patient.

Drug delivery device 1802 may be any drug delivery device that can beused for administering a medication to a subject. For example, drugdelivery device 1802 may be an injection pen (e.g., an insulin injectionpen), a syringe, a pump (e.g., an insulin delivery pump), an ampoule,and/or a vial. Dose measurement system 1800 may be configured to becoupleable to a wide variety of drug delivery devices having, forexample, different shapes, sizes, and drug volumes. In some embodiments,dose measurement system 1800 may be configured to receive a portion ofdrug delivery device 1802, the portion defining an internal volumeincluding the drug, an injector, and/or a plunger. In some embodiments,dose measurement system 1800 is configured to be removable from drugdelivery device 1802 when the user is delivering a dose to target T. Insome embodiments, dose measurement system 1800 can remain attached todrug delivery device 1802 when the user is delivering a dose to thetarget T. In some embodiments, dose measurement system 1800 isconfigured to be reusable. In some embodiments, dose measurement system1800 is permanently coupled to drug delivery device 1802, for example,integrated into the body of the drug delivery device. In suchembodiments, dose measurement system 1800 may be disposable.

Lighting module 1804 and sensing module 1806 may be configured asdescribed above according to some embodiments. For example, lightingmodule 1804 may include a plurality of light sources configured to emitelectromagnetic radiation towards drug delivery device 1802. Sensingmodule 1806 may include a plurality of sensors that are opticallycoupleable to the plurality of light sources of lighting module 1804.

Processing unit 1808 may be configured as described above according tosome embodiments. For example, processing unit 1808 may be configured toreceive the electromagnetic radiation signal from sensing module 1806(i.e., from each of the plurality of sensors) and convert the receiveddata into a signal signature representative of the electromagneticradiation detected by each of the plurality of sensors.

Temperature sensing module 1810 may be configured to measure atemperature of a liquid disposed within drug delivery device 1802 and/orthe environment around the liquid, for example, an internal volume of ahousing within which the components of dose measurement system 1800 andat least a portion of drug delivery device 1802 are disposed, asdescribed herein. Temperature sensing module 1810 may include one ormore suitable temperature sensors, including, but not limited to,thermocouples, resistive temperature devices (RTDs), thermistors,bimetallic temperature sensors, and/or silicon diodes.

One or more temperature sensors may be positioned, configured, attachedto, and/or disposed within dose measurement system 1800 forsubstantially accurate temperature readings of the liquid and/or theenvironment surrounding the liquid. For example, a temperature sensormay be positioned a sufficient distance from one or more components ofdose measurement system 1800 that could impact temperature readings,such as higher temperature electronics (e.g., included in processingunit 1808), a power source (e.g., a rechargeable battery), and/or anyother heat generating electronics. Furthermore, a temperature sensor maybe positioned in sufficient proximity to the liquid disposed in drugdelivery device 1802 to allow heat to diffuse equally to the temperaturesensor and the liquid such that the temperature sensor and the liquidare at substantially the same temperature.

In some embodiments, temperature sensing module 1810 includes a singletemperature sensor. In other embodiments, temperature sensing module1810 includes a plurality of temperature sensors positioned in anysuitable configuration, including, but not limited to, a straight row, arectangular array, a square array, a circular array, and/or any othersuitable configuration. In some embodiments, temperature sensing module1810 includes a first temperature sensor or a first set of temperaturesensors positioned and/or configured to measure a temperaturesubstantially of the liquid, and a second temperature sensor or a secondset of temperature sensors positioned and/or configured to measure atemperature substantially of the environment surrounding the liquid.

In some embodiments, temperature sensing module 1810 includes a printedcircuit board (PCB) and/or other electronics configured to process thetemperature measurement and/or communicate the temperature informationto, for example, processing unit 1808 and/or communications module 1812for further processing and/or to communicate a temperature measurementto a user.

In some embodiments, temperature sensing module 1810, processing unit1808, and/or an external computing device process temperature data.Temperature data may be used to determine one or more properties of aliquid and/or an environment surrounding the liquid in dose measurementsystem 1800, including one or more properties of embodiments of thesystems, apparatus, and methods described herein.

In particular, temperature may affect signal quality (e.g., measurementsof a quantity of a liquid using sensing module 1806) according to someembodiments. Temperature data may be used to normalize data receivedfrom sensing module 1806 such that the sensor data is substantially freeof any artifacts or contribution caused by extreme temperatures and/ortemperature changes or fluctuations. Due to component changes overtemperature, optical measurement sensor readings drift overtemperatures. In some embodiments, this sensor drift over temperature issubstantially linear. In some embodiments, the lighting module 1804 andsensing module 1806 are optimized to maintain substantially linearsensor drift over temperature.

In some embodiments, temperature sensing module 1810, processing unit1808, and/or an external computing device may be used to perform atemperature calibration. For example, an external temperaturemeasurement system that includes an independent temperature sensor maybe used to obtain a calibration temperature. A positive offset or anegative offset may be calculated based on a difference between anexternal calibration temperature and an internal temperature measured bya temperature sensor in temperature sensing module 1810. The positiveoffset or the negative offset may be added to future internaltemperature readings.

Extreme temperatures and/or temperature changes or fluctuations may alsoaffect one or more properties of a liquid or a component of the liquidbeing measured as well as one or more properties of an additionalcomponent of or associated with some embodiments, such as accuracy of aglucose meter test strip or glucometer. For example, thebioavailability, bioefficacy, and shelf life of a medication are highlydependent on the temperatures to which the medication is exposed and/orat which the medication is stored. Drug delivery devices, particularlyinjection pens, that contain such medications or additional componentsare often carried by a patient, for example, in the patient's pocket,backpack, purse, luggage, etc. Thus, medications may be exposed towidely varying ambient temperatures with impacts on at least theadministration, cost, and safety associated with said medications.

For example, the effectiveness of insulin may be degraded by hightemperatures. If a patient is dosed with ineffective insulin, he or shemay develop hyperglycemia. Manufacturers instruct users to discardinsulin that has been exposed to such high temperatures, which happensfrequently by accident. Even though the ambient temperature may be belowa maximum threshold temperature to preserve quality (e.g., higher thanabout 37° C. or 98.6° F.), the temperature of the insulin itself mayexceed ambient temperature when its container is exposed to sunlight orradiant heat. The maximum threshold temperature to preserve quality maychange (e.g., be lower) once the container has been opened (e.g., higherthan about 30° C. or 86° F.). Similarly, insulin quality may be affectedby low temperatures. For example, manufacturers instruct users not tostore insulin in a refrigerator once the container has been opened.

According to some embodiments, guidelines like a maximum thresholdtemperature, a minimum threshold temperature, a range of temperature, arate of temperature change, a frequency of temperature fluctuations,and/or a time period of temperature exposure is recommended, allowed,and/or determined to be acceptable based on at least one of theparticular liquid measurement system (e.g., dose measurement system1800), the particular liquid container (e.g., drug delivery device1802), and the particular liquid (e.g., insulin). Temperature sensingmodule 1810, processing unit 1808, and/or an external computing devicemay be configured to compare one or more temperature readings from aliquid and/or its environment to these metrics to determine whether auser should be notified, for example, via an indication, alert, and/oralarm (e.g., via communications module 1812), that, for example, apredetermined number of temperature readings: (1) have exceeded arecommended, allowed, and/or determined maximum threshold temperaturevalue; (2) have dropped below a recommended, allowed, and/or determinedminimum threshold temperature value; (3) are outside a recommended,allowed, and/or determined range of temperature values; (4) indicate arate of temperature change that exceeds a recommended, allowed, and/ordetermined rate; (5) indicate a frequency of temperature fluctuationsthat exceeds a recommended, allowed, and/or determined frequency; and/or(6) indicate a time period of temperature exposure longer than isrecommended, allowed, and/or determined to be acceptable.

Communications module 1812 may be configured as described aboveaccording to some embodiments. For example, communications module 1812may be configured to allow two-way communication with a user and/or anexternal device. In some embodiments, communications module 1812includes a display configured to communicate a status of dosemeasurement system 1800 to the user, including, but not limited to, doseremaining, history of use, remaining battery life, wireless connectivitystatus, temperature of a drug, temperature of dose measurement system1800, temperature of drug delivery device 1802, efficacy of the drug,expiration status of the drug, quality of the drug, and/or a reminder toadminister the drug.

Dose measurement system 1800 may be disposed in a housing that can beconfigured to be removably coupleable to drug delivery device 1802. Forexample, lighting module 1804, sensing module 1806, processing unit1808, temperature sensing module 1810, and communications module 1812may be incorporated into a housing. Alternatively, individual componentsof dose measurement system 1800 (e.g., lighting module 1804 and sensingmodule 1806) may be incorporated into a first housing and othercomponents (e.g., processing unit 1808, temperature sensing module 1810,and communications module 170) may be separate or incorporated into asecond housing. In some embodiments, a housing is configured (e.g.,shaped and sized) to be removably coupled to at least a portion of drugdelivery device 1802. For example, the housing may have a recess and/ormay define a bore into which at least a portion of drug delivery device1802 can be received.

Having described above various general principles, several exemplaryembodiments of these concepts are now described. These embodiments areonly examples, and many other configurations of a liquid measurementsystem, particularly a dose measurement system for measuring dosedelivered to a patient and/or remaining in a drug delivery device, thataccount for temperature effects are envisioned.

Referring now to FIGS. 19-22, a liquid measurement system 2000 (alsoreferred to herein as “dose measurement system 2000”) may include asensing assembly 2002, a temperature sensing module 2004, acommunications module 2006, and a power source 2008 according to someembodiments. FIG. 19 is a perspective view of liquid measurement system2000. FIG. 20 is an exploded perspective view, FIG. 21 is a backperspective view of a bottom housing, and FIG. 22 is a bottom view of aPCB included in sensing assembly 2002 of dose measurement system 2000.

Dose measurement system 2000 may be configured to be removablycoupleable to a drug delivery device 2010 (also referred to herein as an“injection pen 2010”). Drug delivery device 2010 may be configured todeliver a predefined quantity (i.e., dose) of a liquid drug (e.g.,insulin) to a patient. Examples of drug delivery device 2010 includeinsulin injection pens that may be used by a patient to administerinsulin. According to some embodiments, as shown in FIG. 20, drugdelivery device 2010 includes a housing 2012, an actuator 2014, and aninjector 2016. Housing 2012 may be relatively opaque, such that it onlyallows select wavelengths of electromagnetic radiation (e.g., infraredor microwave radiation) to be transmitted there through. Housing 2012may define an internal volume (e.g., a reservoir) for storing a drug.Actuator 2014 may include a plunger portion in fluid communication withthe drug and configured to communicate a predefined quantity of the drugto the patient. Actuator 2014 may be configurable, for example, by theuser, to dispense variable quantities of the drug. Injector 2016, (e.g.,a needle) may be configured to penetrate a user's tissue forintramuscular, subcutaneous, and/or intravenous delivery of the drug.Housing 2012 may be configured such that temperature sensing module 2004can measure a temperature of the drug directly or indirectly via housing2012, actuator 2014, and/or injector 2016.

In some embodiments, and as shown in FIG. 19, dose measurement system2000 includes a housing 2018 that includes a top housing portion 2020(also referred to herein as “top housing 2020”) and a bottom housingportion 2022 (also referred to herein as “bottom housing 2022”). Tophousing portion 2020 includes a first portion 2020 a and a secondportion 2020 b that may be coupled together to the form the top portion2020. The first portion 2020 a and the second portion 2020 b may beremovably or fixedly coupled together by, for example, gluing, hotwelding, a snap-fit mechanism, one or more screws, and/or by any othersuitable means. Furthermore, the top housing 2020 and bottom housing2022 may be removably or fixedly coupled together by, for example,gluing, hot welding, mechanical coupling (e.g., one or more snap-fitmechanisms or screws), and/or by any other suitable coupling means.

Housing 2018 may be made from a rigid, lightweight, and/or opaquematerial, including, but not limited to, polytetrafluoroethylene, highdensity polyethylene, polycarbonate, other plastics, acrylic, sheetmetal, any other suitable material, or a combination thereof. Housing2018 also may be configured to shield the internal electronic componentsof dose measurement system 2000 from environmental electromagneticnoise. For example, housing 2018 may include an insulation structuresuch as, for example, aluminum lining or any other metal sheet or foilthat can serve as an electromagnetic shield.

As shown in FIG. 19, first housing portion 2022 a and second housingportion 2022 b may define an internal volume for substantially housingsensing assembly 2002, temperature sensing module 2004, communicationsmodule 2006 and power source 2008. As shown in FIG. 21, bottom housingportion 2022 may define a bore 2024. Bore 2024 may be shaped and sizedto receive at least a portion of drug delivery device 2010. For example,bore 2024 may be shaped and sized to receive only the drug-containingportion of housing 2012 and injector 2016. Bore 2024 may be configuredto receive drug delivery device 2010 in a particular orientation (e.g.,a radial orientation). In some embodiments, bore 2024 is in closetolerance with a diameter of drug delivery device 2010, for example, toform a friction fit with drug delivery device 2010. In some embodiments,bore 2024 includes one or more notches, grooves, detents, snap-fitmechanisms, threads, and/or other coupling mechanisms for removablycoupling drug delivery device 2010 to the bottom housing 2022. In someembodiments, bottom housing portion 2022 includes one or more alignmentfeatures for removably coupling drug delivery device 2010 to becoupleable with dose measurement system 2000 in a predetermined radialorientation.

In some embodiments, bottom housing 2022 defines one or more apertures2026 for receiving at least a portion of a plurality of light sourceswhich may be included in a lighting module of the sensing assembly 2002,and/or sensors including in a sensing module of the sensing assembly2002. The one or more apertures 2026 may be configured to providemechanical support for the light sources and/or sensors, and may serveas an alignment mechanism for the lighting and/or sensing modules.

As shown in FIG. 19, top housing 2020 may define an opening 2028 forreceiving at least a portion of communications module 2006, such as, forexample, a communication interface to provide wired communication withan external device, and/or an interface for charging power source 2008.As shown in FIGS. 19 and 20, top housing 2020 may define a slot 2030 forviewing a display 2032 included in communications module 2006, asdescribed herein. A transparent layer 2034, such as, for example, aglass, acrylic (e.g., Plexiglas®), or plastic sheet, may be disposedbelow the slot 2030 to protect the display 2032 and to provide a windowfor viewing the display 2032.

In some embodiments, housing 2018 also includes a detection mechanism(not shown) to detect if drug delivery device 2010 has been coupled todose measurement system 2000. The detection mechanism may include, forexample, a push switch, a motion sensor, a position sensor, an opticalsensor, a piezoelectric sensor, an impedance sensor, and/or any othersuitable sensor. Housing 2018 may be relatively smooth and free of sharpedges. In some embodiments, housing 2018 is shaped to resemble a pen capthat has a form factor that occupies minimal space, for example, can fitin the pocket of a user. In some embodiments, housing 2018 also includesfeatures, for example, clips for attaching to a user's shirt pocket,and/or other ornamental features. In some embodiment, dose measurementsystem 2000 also serves as a replacement cap for drug delivery device2010.

Sensing assembly 2002 may include a lighting module, a sensing module,and a processing unit which may be configured to determine a doseremaining in drug delivery device 2010. Sensing assembly may include aprinted circuit board (PCB) 2034 on which the lighting module, thesensing module, and the processing unit may be mounted, as shown in FIG.22. The lighting module and the sensing module may be substantiallysimilar to lighting module 1804 and sensing module 1806 described withrespect to dose measurement system 1800, as described above.Furthermore, the processing unit may be substantially similar toprocessing unit 1808, as described above.

In some embodiments, the lighting module includes a plurality of lightsources 2036 disposed on the PCB 2034 which may be configured to producean electromagnetic radiation of a wavelength that is capable ofpenetrating through housing 2012 of drug delivery device 2010, the drugcontained therein, and/or a portion of housing 2018. For example,infrared radiation or microwave radiation can penetrate many of theplastic materials that are commonly used in manufacturing drug deliverydevices (e.g., injection pens). In some embodiments, an electromagneticradiation has a frequency that can penetrate through the internalcomponents of drug delivery device 2010, for example, the plungerportion of actuator 2014. In some embodiments, the light sources 244 areconfigured to produce a wide beam of electromagnetic radiation, forexample, wide angle LEDs or a single LED connected to a light pipesplitting emitted electromagnetic radiation into a plurality of wideangle beams). Said another way, the electromagnetic radiation cone of asingle light source 244 can have a wide angle and the electromagneticradiation cones of adjacent light sources 244 can overlap. In someembodiments, the plurality of light sources 2036 are configured to emitpulses of electromagnetic radiation (e.g., a series of less than 100microsecond pulses).

The sensing module may include a plurality of sensors 2038 which may bemounted, or otherwise disposed on, the PCB 2034 included in the sensingmodule 230, as shown in FIG. 5. The PCB 252 may be any standard PCB madeby any commonly known process. The plurality of sensors 2038 may be anyoptical sensors (e.g., photodiodes) optically coupleable with theplurality of light sources 2036 and configured to detect at least aportion of the electromagnetic radiation emitted by the plurality oflight sources 2036. The electromagnetic radiation may be transmittedradiation, refracted radiation (refracted by, e.g., air, drug, and/orbody of drug delivery device 2010), reflected radiation (reflected from,e.g., a wall of housing 2018 or internally reflected from a wall of drugdelivery device 2010), and/or multi-directional refraction/reflection(caused by, e.g., a lensing effect of a curved surface of housing 2012).The transmitted, refracted, and/or reflected electromagnetic signalreceived by the plurality of sensors 2038 may be used to create a signalsignature (e.g., by the processing unit). The signal signature may beassociated with a reference signature to determine the dose remaining indrug delivery device 2010. In some embodiments, the signal response ofthe sensors 2038 may be used to measure usability metrics such asdetermining, for example, the presence of injector 2016 of drug deliverydevice 2010 and/or whether drug delivery device 2010 is coupled oruncoupled with dose measurement system 2000. In some embodiments, thesignal response of the sensors 2038 may be processed further (e.g.,calibrated) based on temperature data.

Temperature sensing module 2004 may include one or more temperaturesensors configured to measure the temperature of the liquid disposedwithin drug delivery device 2010 and/or the environment around theliquid, for example, the internal volume of bore 2024 of bottom housing2022 within which at least a portion of drug delivery device 2010 may bedisposed. The one or more temperature sensors may include one or morethermocouples, RTDs, thermistors, bimetallic temperature sensors,silicon diodes, and/or any other suitable temperature sensors. One ormore temperature sensors may be positioned and/or disposed in theinternal volume defined by top housing 2020 a to allow substantiallyaccurate temperature readings of the liquid volume and/or theenvironment surrounding the liquid. For example, the one or moretemperature sensors may be disposed along an outer surface of a sidewallof bottom housing 2020 b.

Furthermore, one or more temperature sensors may be positioned asufficient distance away from any components of dose measurement system2000 that can impact temperature readings such as, for example, highertemperature electronic component 2040 (e.g., a capacitor or resistor) orpower source 2008 as shown in FIG. 20. Furthermore, one or moretemperature sensors may be disposed in sufficient proximity to theliquid volume disposed in drug delivery device 2010 so that thediffusion of heat to the one or more temperature sensors and the liquidis substantially equal and the one or more sensors accurately reflectthe temperature of the liquid. In some embodiments, temperature sensingmodule 2004 includes a first temperature sensor or a first set oftemperature sensors configured to solely measure the temperature of theliquid, and a second temperature sensor or a second set of temperaturesensors configured to solely measure the temperature of the environmentsurrounding the liquid. In some embodiments, temperature sensing module2004 consists of a single temperature sensor. In other embodiments,temperature sensing module 2004 includes a plurality of temperaturesensors disposed in, for example, a straight row, a rectangular array, asquare array, a circular array, or any other suitable configuration. Insome embodiments, temperature sensing module 2004 includes a printedcircuit board (PCB) and/or other electronics configured to process dataand/or communicate temperature data to, for example, communicationsmodule 2006.

In some embodiments, temperature sensing module 2004 includes aprocessing unit. In some embodiments, temperature sensing module 2004 isconfigured to communicate temperature data to the processing unitincluded in the sensing assembly 2002. At least one processing unit isconfigured to use the temperature data to determine a quality of theliquid (e.g., a bioavailability, bioefficacy, and/or expiration statusof one or more components) and/or a quality of administration (e.g., alevel of ease and/or comfort). For example, information on thermalstability and efficacy of a liquid drug disposed in drug delivery device2010 may be stored in memory coupled to a processing unit. Theprocessing unit may compare a real-time temperature of the liquid drugand/or the environment surrounding the drug provided by temperaturesensing module 2004 with the thermal stability information for theparticular drug to determine a physical and/or chemical status/qualityof the drug. In some embodiments, thermal stability information for amultitude of drugs (e.g., insulin, epinephrine, etc.) or just aparticular drug may be stored in an external or internal memory devicecommunicatively coupled to the processor, thereby allowing dosemeasurement system 2000 to be compatible with different drug deliverydevices that may contain different drugs, a particular drug deliverydevice that may contain different drugs, different drug delivery devicesthat contain a substantially similar drug, or a particular drug deliverydevice that contains a substantially similar drug.

In some embodiments, temperature data is used to normalize or correctdata received from the sensing module so that the sensor data (i.e., thesignal signature) is substantially free of any artifacts orcontributions caused by extreme temperatures, temperature changes,and/or temperature fluctuations.

FIG. 23 is a graph showing compensated measurements 2300 anduncompensated measurements 2302 of a representative sensor of a liquidmeasurement system as a function of temperature in accordance with someembodiments. The uncompensated sensor measurements 2302 may divergesubstantially from actual temperature as the actual temperature changesand/or fluctuates. In some embodiments, it may be preferable to adjusttemperature measurements as the actual temperature changes and/orfluctuates, thereby generating compensated measurements 2300 in order tomore accurately monitor the real temperature of the remaining liquid.

In some embodiments, compensation for temperature change is achieved byapplying the following correction factor:

A×ΔT×S _(raw)  (1)

where A is a scaling constant that may vary according to the individualsensor design, S_(raw) is the unprocessed sensor reading, and ΔT is thedifference between the measured temperature and a baseline temperature,which may be any temperature (e.g., 0° C.) as long as it remainsconstant:

ΔT=T _(meas) −T _(base)  (2)

Thus, a compensated sensor value may be determined according to:

S _(comp) =S _(raw) +A×ΔT×S _(raw)  (3)

In some embodiments, the scaling constant accounts for saturation edgecases. If a particular sensor is already saturated, the sensor may notbe allowed to be under saturated due to temperature compensation.

Temperature data also may be used to normalize the calibrationsignature, for example, if the calibration was performed at a firsttemperature, and the signal signature is measured at a secondtemperature different from the first temperature. In some embodiments,sensor data is normalized with respect to the thermal expansioncoefficient of the drug using the temperature data. In this manner anyerrors due to volumetric expansion or contraction of the liquid drug orother temperature-related interference with the sensor may be corrected.

In some embodiments, a processing unit is configured to performtemperature calibrations. For example, in such embodiments, theprocessing unit may be configured to receive a calibration temperaturemeasured by an external temperature measurement system that includes anindependent temperature sensor. A positive offset or a negative offsetmay be generated based on the difference between the externalcalibration temperature and an internal temperature measured by thetemperature sensor included in temperature sensing module 2004. For anyfuture temperature sensing, the processing unit can then calculate thefinal temperature reading by adding the positive offset or the negativeoffset to the internal temperature.

Placement of a temperature sensor is important to accurate temperaturecompensation and/or calibration. In some embodiments, a temperaturesensor is placed in close proximity to the components that most varyover temperature. In some embodiments, the component that varies mostover temperature is an emitters or light source. In FIG. 24 a diagram ofpart of a dose measurement system shows a temperature sensor 2400 placedin close proximity to the light sources 2402 (e.g., a plurality of LEDsor a single LED connected to a light pipe splitting emittedelectromagnetic radiation into the plurality of light sources) inaccordance with some embodiments.

Temperature is also a key factor affecting blood glucose measurement.The temperature(s) at which test strips are stored and at which aglucose meter or glucometer is operated are both important. Inparticular, temperature may affect the response of electronics in aglucometer, similar to a dose measurement system, as described above.Temperature also may affect the kinetics of chemical reaction on a teststrip. Thus, a temperature sensor placed in close proximity to aglucometer and/or a test strip is important according to someembodiments.

In some embodiments, a glucometer is communicatively coupled and/orphysically coupled with a dose measurement system (e.g., integratedwithin the housing). One or more temperature sensors may be placed on orin proximity to the glucometer in order to compensate blood glucosemeasurements for drift over temperature. In some embodiments, aremovable and/or refillable test strip storage device is communicativelycoupled and/or physically coupled with a dose measurement system (e.g.,integrated within the housing) and/or a glucometer communicativelycoupled and/or physically coupled with the dose measurement system. Oneor more temperature sensors may be placed on or in proximity to thestorage device in order to identify quality issues relating to teststrip temperature exposure.

In some embodiments, a communication interface on a dose measurementsystem or on an external device communicatively coupled with a dosemeasurement system is configured to communicate a status of the dosemeasurement system to the user, including, but not limited to, doseremaining, history of use, remaining battery life, wireless connectivitystatus, user reminders, and/or temperature measurements. A display,speaker, and/or vibration mechanism may be used to convey visual, audio,and/or tactile indications or alerts to a user. In some embodiments, auser input interface (e.g., a button, a switch, an alphanumeric keypad,a touch screen, a camera, and/or a microphone) allows a user to inputinformation or instructions into a dose measurement system, including,but not limited to, initiating or ending communication between thesystem and a remote device, powering ON the system, powering OFF thesystem, resetting the system, manually inputting details of a patientbehavior, and/or manually inputting details of drug delivery deviceusage.

FIG. 26 is a screenshot of a user interface display on a remote device(e.g., a smart phone) for initiating or ending communication between thedevice and one or more dose measurement systems and, once communicationis initiated, for monitoring the remaining volume, battery life, andtemperature of each of one or more dose measurement systems inaccordance with some embodiments.

In some embodiments, when a temperature exceeds the recommended,allowed, and/or determined operating range for a drug, a user mayreceive a notification from the system or from an external devicecommunicatively coupled with the system. The notification may requireaction by the user to be dismissed. In some embodiments, a time displaytracks when a temperature event has occurred. Thus, a user may reviewany notifications and/or the time display to identify any temperatureevents in order to recalibrate the system or dispose of a drug or teststrip.

CONCLUSION

While various inventive embodiments have been described and illustratedherein, those of ordinary skill in the art will readily envision avariety of other means and/or structures for performing the functionand/or obtaining the results and/or one or more of the advantagesdescribed herein, and each of such variations and/or modifications isdeemed to be within the scope of the inventive embodiments describedherein. More generally, those skilled in the art will readily appreciatethat all parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the inventive teachingsis/are used. Those skilled in the art will recognize, or be able toascertain using no more than routine experimentation, many equivalentsto the specific inventive embodiments described herein. It is,therefore, to be understood that the foregoing embodiments are presentedby way of example only and that, within the scope of the appended claimsand equivalents thereto, inventive embodiments may be practicedotherwise than as specifically described and claimed. Inventiveembodiments of the present disclosure are directed to each individualfeature, system, article, material, kit, and/or method described herein.In addition, any combination of two or more such features, systems,articles, materials, kits, and/or methods, if such features, systems,articles, materials, kits, and/or methods are not mutually inconsistent,is included within the inventive scope of the present disclosure.

Where methods and steps described above indicate certain eventsoccurring in certain order, those of ordinary skill in the art havingthe benefit of this disclosure would recognize that the ordering ofcertain steps may be modified and such modification are in accordancewith the variations of the invention. Additionally, certain of the stepsmay be performed concurrently in a parallel process when possible, aswell as performed sequentially as described above. The embodiments havebeen particularly shown and described, but it will be understood thatvarious changes in form and details may be made.

For example, although various embodiments have been described as havingparticular features and/or combination of components, other embodimentsare possible having any combination or sub-combination of any featuresand/or components from any of the embodiments described herein. Forexample, although some embodiments were described as having a dosemeasurement system that resembled a pen cap, the dose measurement systemalso may be integrated with a drug delivery device. In some embodiments,vibration and/or ultrasonic waves are used to generate the signalsignature instead of electromagnetic radiation. In addition, thespecific configurations of the various components also may be varied.For example, the size and specific shape of the various components maybe different than the embodiments shown, while still providing thefunctions as described herein.

The above-described embodiments can be implemented in any of numerousways. For example, embodiments disclosed herein may be implemented usinghardware, software or a combination thereof. When implemented insoftware, the software code can be executed on any suitable processor orcollection of processors, whether provided in a single computer ordistributed among multiple computers.

Further, it should be appreciated that a computer may be embodied in anyof a number of forms, such as a rack-mounted computer, a desktopcomputer, a laptop computer, or a tablet computer. Additionally, acomputer may be embedded in a device not generally regarded as acomputer but with suitable processing capabilities, including a PersonalDigital Assistant (PDA), a smart phone or any other suitable portable orfixed electronic device.

Also, a computer may have one or more input and output devices. Thesedevices can be used, among other things, to present a user interface.Examples of output devices that can be used to provide a user interfaceinclude printers or display screens for visual presentation of outputand speakers or other sound generating devices for audible presentationof output. Examples of input devices that can be used for a userinterface include keyboards, and pointing devices, such as mice, touchpads, and digitizing tablets. As another example, a computer may receiveinput information through speech recognition or in other audible format.

Such computers may be interconnected by one or more networks in anysuitable form, including a local area network or a wide area network,such as an enterprise network, and intelligent network (IN) or theInternet. Such networks may be based on any suitable technology and mayoperate according to any suitable protocol and may include wirelessnetworks, wired networks or fiber optic networks.

The various methods or processes outlined herein may be coded assoftware that is executable on one or more processors that employ anyone of a variety of operating systems or platforms. Additionally, suchsoftware may be written using any of a number of suitable programminglanguages and/or programming or scripting tools, and also may becompiled as executable machine language code or intermediate code thatis executed on a framework or virtual machine.

Also, various inventive concepts may be embodied as one or more methods,of which an example has been provided. The acts performed as part of themethod may be ordered in any suitable way. Accordingly, embodiments maybe constructed in which acts are performed in an order different thanillustrated, which may include performing some acts simultaneously, eventhough shown as sequential acts in illustrative embodiments.

All publications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety.

All definitions, as defined and used herein, should be understood tocontrol over dictionary definitions, definitions in documentsincorporated by reference, and/or ordinary meanings of the definedterms.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of.” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03.

1. An apparatus for measuring liquid volume in a container, theapparatus comprising: a plurality of light sources disposed andconfigured to emit electromagnetic radiation toward the container; aplurality of sensors optically coupleable to the plurality of lightsources, each sensor of the plurality of sensors disposed and configuredto detect the electromagnetic radiation emitted by at least a portion ofthe plurality of light sources; a temperature sensor disposed andconfigured to measure at least one temperature associated with a liquidin the container; and at least one processor configured to receive datarepresentative of the portion of the detected electromagnetic radiationfrom each of the plurality of sensors and the at least one measuredtemperature from the temperature sensor, the processor operable to:compare the at least one measured temperature to a temperature guidelineto identify any temperature events associated with the received data;normalize the received data based on any temperature events associatedwith the received data; and convert the normalized data into a signaturerepresentative of the electromagnetic radiation detected by theplurality of sensors.
 2. The apparatus of claim 1, wherein thetemperature guideline includes at least one of a baseline temperature, amaximum temperature, and a minimum temperature.
 3. The apparatus ofclaim 2, wherein the temperature guideline further includes at least oneof an amount of one-time exposure above the maximum temperature and theminimum temperature, an amount of one-time exposure below the minimumtemperature, an amount of cumulative exposure above the maximumtemperature, an amount of cumulative exposure below the minimumtemperature, a maximum rate of temperature change, and a maximumfrequency of temperature fluctuations.
 4. The apparatus of claim 1,wherein the temperature guideline is specific to at least one of theapparatus, the container, and the liquid.
 5. The apparatus of claim 1,wherein a temperature event is at least one of a relationship and adifference between the at least one measured temperature and the atleast one temperature guideline.
 6. The apparatus of claim 1, furthercomprising a memory configured to store at least one of: the at leastone measured temperature; and the temperature guideline.
 7. Theapparatus of claim 1, wherein the at least one processor is furtherconfigured to determine at least one of a level of efficacy, a level ofsafety, a level of subject comfort, and an expiration status associatedwith the liquid based on any temperature events associated with thereceived data.
 8. The apparatus of claim 7, further comprising at leastone communication interface configured to communicate informationassociated with the at least one of the level of efficacy, the level ofsafety, the level of subject comfort, and the expiration statusassociated with the liquid to a user.
 9. The apparatus of claim 1,further comprising a glucometer configured to measure blood glucose of asubject, wherein the at least one processor is further configured to:receive a blood glucose measurement; and normalize the blood glucosemeasurement based on any temperature events associated with the bloodglucose measurement.
 10. A method of estimating a volume of liquid in adrug container, the method comprising: causing a plurality of lightsources to emit electromagnetic radiation toward the drug container;detecting the emitted electromagnetic radiation through the drugcontainer with a plurality of sensors; measuring at least onetemperature associated with the liquid in the drug container with atemperature sensor; comparing the at least one measured temperature to atemperature guideline to identify any temperature events associated withthe detected electromagnetic radiation; normalizing data representativeof the portion of the detected electromagnetic radiation from each ofthe plurality of sensors based on any temperature events associated withthe detected electromagnetic radiation; converting the normalized datainto a signature representative of the electromagnetic radiationdetected by the plurality of sensors; and comparing the signature to aplurality of reference signatures to determine the volume of liquid inthe drug container.
 11. The method of claim 10, wherein the temperatureguideline includes at least one of a baseline temperature, a maximumtemperature, and a minimum temperature.
 12. The method of claim 11,wherein the temperature guideline further includes at least one of anamount of one-time exposure above the maximum temperature and theminimum temperature, an amount of one-time exposure below the minimumtemperature, an amount of cumulative exposure above the maximumtemperature, an amount of cumulative exposure below the minimumtemperature, a maximum rate of temperature change, and a maximumfrequency of temperature fluctuations.
 13. The method of claim 10,wherein the temperature guideline is specific to at least one of theapparatus, the container, and the liquid.
 14. The method of claim 10,wherein a temperature event is at least one of a relationship and adifference between the at least one measured temperature and the atleast one temperature guideline.
 15. The method of claim 10, furthercomprising storing at least one of: the at least one measuredtemperature; and the temperature guideline.
 16. The method of claim 10,further comprising determining at least one of a level of efficacy, alevel of safety, a level of subject comfort, and an expiration statusassociated with the liquid based on any temperature events associatedwith the received data.
 17. The method of claim 16, further comprisingcommunicating information associated with the at least one of the levelof efficacy, the level of safety, the level of subject comfort, and theexpiration status associated with the liquid to a user.
 18. The methodof claim 10, further comprising: measuring a blood glucose level of asubject; and normalizing the blood glucose measurement based on anytemperature events associated with the blood glucose measurement.
 19. Amethod, comprising: causing a plurality of light sources to emitelectromagnetic radiation toward an injection pen a first time;detecting the emitted electromagnetic radiation through the injectionpen with a plurality of sensors; measuring at least one temperatureassociated with a liquid in the injection pen with a temperature sensor;comparing the at least one measured temperature to a temperatureguideline to identify any temperature events associated with thedetected electromagnetic radiation; normalizing data representative ofthe portion of the detected electromagnetic radiation from each of theplurality of sensors based on any temperature events associated with thedetected electromagnetic radiation; converting the normalized data intoa first signature representative of the electromagnetic radiationdetected by the plurality of sensors; comparing the first signature to aplurality of reference signatures to determine a first volume of liquidin the injection pen; repeating the steps of causing the plurality oflight sources to emit electromagnetic radiation, detecting the emittedelectromagnetic radiation, measuring at least one temperature associatedwith a liquid in the injection pen, comparing the at least one measuredtemperature to a temperature guideline to identify any temperatureevents associated with the detected electromagnetic radiation,normalizing data representative of the portion of the detectedelectromagnetic radiation from each of the plurality of sensors based onany temperature events; and converting the normalized data into a secondsignature, and comparing the second signature to the plurality ofreference signatures to determine a second volume of liquid in theinjection pen; and estimating a dose delivered from the injection penbased on the first volume and the second volume.
 20. (canceled)